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The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction. We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%). Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients’ group (Spearman rho = −0.68, P=0.00094). In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD.

Recent studies have shown the role of mitochondrial DNA (mtDNA) variants in the pathogenesis of both psoriasis (Ps) and type 2 diabetes (T2D) amongst different ethnicities. However, no studies have investigated the mtDNA variants present in patients with Ps, T2D, and both Ps and T2D (Ps-T2D) in the Arab population. The entire mitochondrial genomes of Kuwaiti subjects with Ps, T2D, Ps-T2D and healthy controls were sequenced using Ion Torrent next-generation sequencing. A total of 36 novel mutations and 51 previously reported mutations were identified in the patient groups that were absent in the controls. Amongst the novel mutations, eight were non-synonymous and exhibited amino acid changes. Of these, two missense mutations (G5262A and A12397G) in the ND genes were detected in the Ps group and a C15735T missense mutation in the CYB gene was detected in Ps-T2D. Other known sequence variations were seen more frequently in all or certain patient groups compared with the controls (P

Objective: Published data show a clear link between psoriasis (Ps) and the increasing prevalence of comorbid conditions, such as diabetes mellitus type 2 (DM2). The role of the mitochondrial genomic haplogroup in the potential coexistence of Ps and DM2 comorbidity is the subject of this study. Material and Methods: Ninety-eight Kuwaiti individuals were recruited in 4 cohorts (20 healthy controls, 15 with DM2, 34 with Ps, and 29 with Ps and diabetes mellitus). An Ion Torrent S5XL was used to sequence mitochondrial DNA (mtDNA). χ2 test was used to assess differences in the distribution of each haplogroup between cases and controls (p < 0.05). The Bonferroni correction was applied (p < 0.004). The mtDNA haplogroups were analyzed by HaploGrep. Results: Haplogroups R0, U, J, T, N, L3, M, H, X, HV, R, and K were detected in the studied population. Haplogroup M had a high risk for Ps (odds ratio (OR) 4.0, p = 0.003). Haplogroup R0 and J had decreased the risk of DM2 (OR 0.28, p = 0.007). Conclusion: Our results indicated that mtDNA haplogroups have a potential contribution to the pathogenesis of Ps and DM2 comorbidity. We show for the first time that the comorbidity of diabetes in Ps may be related to mitochondrial dysfunction.

Background Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous blistering skin disease, but in countries such as Kuwait, there are very limited data on the clinical and molecular pathology of EB. To improve understanding of EB in Kuwait, we report the experience of a local tertiary referral center over a 17.5 year period (January 2000-June 2017) in establishing clinical and molecular diagnoses. Methods Review of hospital records and diagnostic reports. Individual cases were diagnosed by combinations of clinical assessment, skin biopsy (immunohistochemistry and transmission electron microscopy), Sanger sequencing of EB genes, and whole exome sequencing. Results Fifty-four families with EB were registered with the clinic over this period, 41 of whom (84 patients) participated in diagnostic studies. Thirty-seven of these 41 families had consanguineous marriages; 34 had recessive forms of EB, while only seven had dominant subtypes. Recurrent mutations were observed in epidermal dystonin, transglutaminase 5, and type VII collagen. Conclusions The prevalence of EB in Kuwait is approximately three times that of internationally cited rates with an over-representation of autosomal recessive variants. Establishing the molecular basis of EB in Kuwait with accurate diagnostic subtyping provides a basis for determining healthcare requirements and improving patient management of EB.

In this study, the potential effect of three HFE gene polymorphisms (C282Y, H63D and S65C) and the SLC40A1 A77D polymorphism on iron balance was investigated in 234 subjects (91 Arab beta-thalassemia major (BTM) patients, 34 beta-thalassemia trait (BTT) individuals and 109 health controls). Genotyping was done using restriction-fragment-length polymorphism and direct-sequencing. Serum-iron, total iron binding capacity, transferrin and ferritin were estimated in all BTT and BTM, and in 65 healthy controls. H63D was the only polymorphism detected in our cohort. Allele frequency was 13% in both BTM and BTT and 10% in controls with no significant difference. Serum iron, ferritin and transferrin saturation were significantly higher in normal males heterozygous for H63D as compared to homozygous wild-type males. Ferritin was significantly higher in BTT males with or without H63D polymorphism when compared to the healthy males with H/H genotype. No such difference was observed between H/H versus H/D BTT subgroups. We conclude that H63D is the only significant hemochromatosis-associated polymorphism in the Arabian Gulf region. The heterozygous state of H63D may significantly alter iron parameters in normal males. In BTT, it appears that the beta-thalassemia allele has an overriding influence on ferritin values, and this generally manifest in males.

The purpose of our study was to identify the currently lacking molecular mechanism that accounts for the co-occurrence of two seemingly disparate diseases: psoriasis and type II diabetes. We aimed to investigate a panel of 84 genes related to the diabetic regulatory network in psoriasis (Ps), psoriasis type II diabetes (Ps-T2D), type II diabetes (T2D) and healthy control (HC). We hypothesize that such attempts would provide novel diagnostic markers and/or insights into pathogenesis of the disease. A quantitative Real Time-PCR Human Diabetes RT2 Profiler PCR Array was chosen to explore the expression profile 84 diabetic genes in study subjects. Statistical analysis was carried out using appropriate software. The analysis revealed three candidate genes GSK3B, PTPN1, STX4 that are differentially expressed in study subjects. GSK3B was highly significant in Ps-T2D (P = 0.00018, FR = − 26.6), followed by Ps (P = 0.0028, FR = − 14.5) and T2D groups (P = 0.032, FR = − 5.9). PTPN1 showed significant association only with PS-T2D (P = 0.00027, FR = − 8.5). STX4 showed significant association with both Ps (P = 0.0002, FR = − 20) and Ps-T2D (P = 0.0016, FR = − 11.2). ACE represents an additional marker that showed suggestive association with Ps (P = 0.0079, FR = − 9.37). Our study highlights the complex genetics of Ps-T2D and present biomarkers for the development of T2D in Ps cases.

The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (-123C/A, -88G/T, -20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 -88G/T SNP and susceptibility to SLE (χ (2) = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03-3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (-123 C, -88 T, -20 A) (χ (2) = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30-14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.

Systemic lupus erythematosus (lupus) is a genetically heterogeneous autoimmune disorder with an obscure etiology. With 92-94% of human genes exhibiting alternative splicing, gaining insights to such events may lead to better diagnostics. Herein, we explored the genome-wide peripheral blood transcriptome of lupus and its severe form lupus-nephritis (LN) compared to healthy controls (HC). Age/gender/ethnically-matched Arab females were tested using high-density arrays and statistical analysis was carried out using appropriate software. Analysis revealed 15 splice variants that are differentially expressed between lupus/HC and 99 variants between LN/HC (p ≤ 0.05, SI> or ≤ 0.5, Benjamin Hochberg-False discovery rate correction). Comparison between LN/lupus revealed 7 variants that significantly differed in expression. Pathway analysis of differentially spliced-genes postulated 11 significant pathways in lupus and 12 in LN (p

Background Systemic lupus erythematosus (lupus) is an autoimmune disease characterized by multiorgan pathology, accelerated apoptosis and hyper-autoantibody production against self-components. The root cause of lupus remains unknown, although multiple susceptibility factors have been reported in different ethnic group. Objective We aimed to explore the genome-wide differential expression spectrum of lupus and its severe form lupus nephritis (LN) in Arab females. Methods A total of 98 subjects: 40 lupus, 18 LN and 40 age/gender/ethnically matched healthy controls (HC) were recruited. Carefully chosen subjects (n = 11) were employed for whole human-genome expression profiling using high-density Human Exon 1.0.ST arrays (Affymetrix) and statistical analysis was carried out using appropriate software. Validation cohorts (n = 98) were investigated to quantify the expression of the nine selected candidate genes relative to GAPDH as endogenous control. Results Genome-wide differential analysis revealed seven candidate genes in lupus and 36 in LN, when individually compared to HC (anova Welch t-test, P ≤ 0.005, Tukey's honestly post hoc analysis). Analysis of differentially expressed genes with a fold change of 2, revealed 16 Gene Ontology terms satisfying a P ≤ 0.05. We further detected five distinct inflammatory and metabolic pathways such as TWEAK, osteopontin, endochondral ossification, fluropyrimidine activity and urea cycle and metabolism of amino groups that significantly contribute to the pathogenesis of lupus (P

OBJECTIVE: We analyzed the Y-chromosome haplogroup diversity in the Kuwaiti population to gain a more complete overview of its genetic landscape. METHOD: A sample of 117 males from the Kuwaiti population was studied through the analysis of 22 Y-SNPs. The results were then interpreted in conjunction with those of other populations from the Middle East, South Asia, North and East Africa, and East Europe. RESULTS: The analyzed markers allowed the discrimination of 19 different haplogroups with a diversity of 0.7713. J-M304 was the most frequent haplogroup in the Kuwaiti population (55.5%) followed by E-M96 (18%). They revealed a genetic homogeneity between the Kuwaiti population and those of the Middle East (FST = 6.1%, P-value

Aim The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort. A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed. Method A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls. Statistical analysis was carried out using the RT2 Profiler TM PCR Data Analysis tool. Results The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC]

Hemophilia is clinically and genetically heterogeneous blood disorder with several known gene defects accounting for the diversity of disease phenotype and inhibitor production. Although increasing number of causative mutations have been reported, not much is known regarding the root cause of inhibitor development against infused blood clotting factors, which represents a major challenge in the treatment of disease. The variations in the severity and frequency of bleeding in hemophiliacs with same molecular defect, indicates the role of modifier genes in the pathogenesis of disease. Herein, we aim to review and summarise the literature over the past decade, to gain insight into what is critical for the development of inhibitors in hemophilia. Aside from potential mutations in factor VIII and IX, polymorphisms in various genes such as human leukocyte antigen-I (HLA-I), HLA-II, tumor necrosis factor-alpha, interleukin-10 and cytotoxic T-lymphocyte associated antigen-4, also tends to contribute to the development of inhibitors. Violating the theory of single gene-single disorder, new research indicates that inhibitor arise from a complex interplay of multiple genetic, immunological and environmental factors. With the revolutionary advances in whole genome sequencing, we propose a detailed genome wide study to identify the spectrum of genetic markers involved in the development of inhibitors for better diagnostics and therapeutics.

Variations in IRF5 have been associated with an increased risk of developing lupus (SLE).To explore the association of IRF5 markers (rs2004640, rs10954213) with susceptibility to SLE and to the development of more than one autoimmune disease (OP) and to analyse the influence of rs2004640 on IRF5 isoform expression.A total of 300 age/gender/ethnicity-matched Kuwaitis were screened using the TaqMan®SNP Genotyping Assay. Data analysis was conducted in three groups: patients with high/low anti-dsDNA antibody titre, lupus nephritis/non-nephritis and disease onset age ≤28 years/28 years. cDNA samples with defined rs2004640 genotypes were amplified using specific primers and transcripts associated with each of the exon1 variants were detected on polyacrylamide-gel.A significant association was observed between the IRF5 markers (rs2004640, rs10954213) and susceptibility to SLE (p0.0001) and OP (p0.025). Stratified analysis showed a significant association of the rs2004640 T-allele with a high titre of anti-dsDNA antibody (p = 0.0035, OR = 1.92) and a low disease onset age ≤28 years (p = 0.0026, OR = 1.94). Additionally, the influential role of the rs2004640 T allele on IRF5 expression was observed.This study is the first to investigate the association of IRF5 markers with OP and the very first to explore the association of these markers with SLE in Arabs. The novelty of this study is the association of the rs2004640 T-allele with increased anti-dsDNA antibody production and SLE in a younger age group.

The purpose of this study was to analyze the effect of the HumDN1 VNTR polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n = 500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1 expression was analysed using quantitative Real-Time-PCR and sera from subjects were screened for DNase1 reduction activity by ELISA. Allele and genotype distribution of HumDN1 VNTR revealed a significant association with susceptibility to SLE and RA (p0.05, OR1). Relative expression analysis revealed a significant increase in DNASE1 mRNA in SLE (p = 0.0001) and RA (p = 0.002) compared to HC. Stratification of subjects revealed, increased DNASE1 expression in SLE with 5/5 (p = 0.0001), 3/4 (p = 0.0001) and 3/5 genotype (p = 0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4 genotype (p = 0.0004). RA patients with 3/4 genotype (p = 0.02) showed a significant increase in DNASE1 expression. Similarly a significant association was observed between DNase1 reduction activity and SLE (p = 0.0001). SLE patients with 3,4 (p = 0.0001) and 5,5 genotype (p = 0.0001) showed increased DNase1 reduction activity, while a lack of association was observed with RA. The present study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in SLE and RA.

The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs -511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C-511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C-511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β -511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61-10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C-511T SNP is linked to the severe form of AA.

Aim: To explore the potential genetic association of CTLA-4 Exon1 +49A/G and 3′UTR (AT)n to susceptibility to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and overlapping (OP) autoimmunity; affected with more than one autoimmune disease. Expression of two major CTLA-4 isoforms; full length (mCTLA-4) and soluble (sCTLA-4) were explored in all subjects. A total of 680-age/gender/ethnically matched Kuwaitis were recruited and polymerase chain reaction (PCR)-fragment analysis was employed for genotyping both markers. mCTLA-4 and sCTLA-4 mRNA expression were analyzed using quantitative real time-PCR. The enzyme-linked immunosorbent assay (ELISA) was used to screen sCTLA-4 in all subjects' sera. Results: Only two CTLA-4 3′UTR (AT)n allelotypes; (AT)15 and (AT)6 were detected. The heterozygous (AT)15/6 genotype confers protectivity rather than susceptibility to SLE (p=0.01, odds ratio=0.43, and confidence interval=0.21–0.86). No significant association was observed between Exon 1 +49A/G and any of the tested diseases. A consistently high serum sCTLA-4 level was observed in RA (6.8 ng/mL, p=0.005), SLE (6.34 ng/mL, p=0.007), and OP (8.75 ng/mL, p=0.012) compared to healthy control. A significant increase in the expression of sCTLA-4 mRNA was observed in OP (p=0.05) and SLE (p=0.047), while a significant increase in the expression of mCTLA-4 (p=0.01) was observed only in OP. Conclusion: The present study is the first to report a statistically significant association between OP and serum sCTLA-4. The novelty of our study is the significance of CTLA-4 in the pathogenesis of OP besides SLE and RA.

To explore the genetic association of single nucleotide polymorphisms (SNPs) in the coding region of the NOTCH4 , exon 3 C+1297T and exon 5 A+3063G, in a case–control analysis of 58 rheumatoid arthritis (RA) and 98 alopecia areata (AA) and 100 ethnically matched healthy subjects. NOTCH4 polymorphisms were genotyped by standard PCR followed by restriction digestion. Analysis of C+1297T SNP revealed a significant association of allele C+1297 ( p = 0.03, OR = 1.66, 95%CI 1.04–2.64) and genotype CT ( p = 0.002, OR = 2.82, 95%CI 1.42–5.59) with susceptibility to RA. Analysis of A+3063G SNP revealed a significant association of allele A+3063 ( p = 0.05, OR = 0.59, 95%CI 0.35–1.008) and genotype AA ( p = 0.002, OR = 0.39, 95%CI 0.17–0.87) with RA. Over all analysis between alopecia patients and the studied SNPs failed to show any significant association. Classifying the patients by severity of disease, confined the risk role of CT genotype to the severest form of alopecia universalis ( p = 0.006, OR = 3.82, 95%CI 1.39–3.82) and AG genotype to semiuniversalis alopecia ( p = 0.004, OR = 4.3, 95%CI 1.5–15.3). Present study is the first to report a statistically significant association between RA and NOTCH4 polymorphisms.

The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production(NOx). Kuwaitis (n= 383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p = 0.0092,OR = 1.76). The 4bb genotype was found to be associated with SLE (p = 0.0076,OR = 1.97) and HT (p = 0.05,OR = 1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p= 0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p= 0.03) and RA (p= 0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p< 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p> 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS – endothelial nitric oxide synthase.

Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3′UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their potential association with HT, and exploring the effect of the tested SNPs on the CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age–gender–ethnically matched subjects were genotyped by fluorescent-labelled restriction fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing was used to confirm the genotyping results. Expression of the full-length and soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and sixteen genotypes of CTLA-4 3′UTR(AT)n. The 3′UTR(AT)n was significantly associated with HT: allele (AT)15 and genotype 15/15 were found to cause susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26–3.58 and P = 0.029, OR = 2.77, 95 % CI = 1.1–6.94, respectively), whereas allele (AT)6 and genotype 6/6 were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227–0.57 and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression of sCTLA-4 was inversely proportional to the number of 3′UTR(AT)n repeats, with heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively). Significant increase in the serum level of sCTLA-4 was observed in HT patients compared with the HC (P = 0.0007). The novel finding in our study is that the CTLA-4 3′UTR(AT)n proven to be a key player in the pathogenesis of HT.

Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤103 copies/µl, intermediate when the viral load = 103–104 copies/µl, and high when the viral load >104 copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. Conclusion: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.

arginine and molecular oxygen in vascular endothelial cells (Kincl et al.2009). Angiotensin-converting enzyme (ACE), present on the surface of vascularendothelial cells, generates the potent vasoconstrictor angiotensin II from angio-tensin I and inactivates the vasodilator bradykinin (Erdo¨s 1990). Angiotensin IImodulates NO synthesis in cardiovascular tissue, and NO modulates the action ofangiotensin II (Dubey et al. 1995; Nakagami et al. 1999). Many polymorphismslocated in the ACE and NOS3 genes have been reported to play a major role in thepathogenesis of coronary artery disease (CAD) and related outcomes (Cambienet al. 1992; Yoshimura et al. 2000; Bor-Kucukatay et al. 2010; Hamelin et al. 2011).The -T786C polymorphism in the NOS3 gene causes a reduction of promoteractivity and has been reported as a risk factor for coronary spasm in a Japanesepopulation (Nakayama et al. 1999). The Glu298Asp polymorphism has been

Endothelial nitric oxide synthase (eNOS) catalyses the production of nitric oxide, which has been shown to participate in the pathogenesis of systemic lupus erythematosus (SLE). eNOS gene polymorphism may have an effect on eNOS gene expression, eNOS protein synthesis and enzymatic activity. We investigated the influence of eNOS gene polymorphisms on susceptibility to SLE. eNOS T-786C, G894T and intron 4 27-base pair tandem repeat (VNTR4) polymorphisms were investigated in 152 SLE patients and 184 controls using RFLP-PCR, direct sequencing and fragment analysis. Allele, genotype and haplotype frequency comparisons, Hardy–Weinberg equilibrium and linkage disequilibrium (LD) analysis were performed. No significant association was detected between SLE and single-nucleotide polymorphisms (SNPs) T-786C and G894T. VNTR4 allele 4b was associated with susceptibility to SLE (OR 1.89, p = 0.023), as was the genotype 4bb (OR 2.41, p = 0.007). However, allele 4a was protective (OR 0.53, p = 0.023), as was genotype 4ab (OR 0.41, p = 0.007). T-786C and VNTR4 were in high LD ( r2 = 0.34). Haplotypes T4bC and C4aG of the three tested polymorphisms had a susceptibility effect on SLE (OR 1.89 and 4.23 at p = 0.005 and 0.001, respectively), while haplotypes T4aG and C4bG had a protective effect (OR 0.06 and 0.11 at p = 0.000001 and 0.0005, respectively). The novel finding in our study is that individual eNOS polymorphisms probably do not exert a major influence on susceptibility to SLE, but they have significant effects when combined within a specific haplotype.

Eur J Clin Invest 2011; 41 (10): 1105–1112 Abstract Background High-density lipoprotein cholesterol (HDL-C) levels are low in Iranians. Low HDL-C is the most frequent phenotype in metabolic syndrome (MetS) among the Iranian population (32%). This has been claimed to be related to genetic factors. Materials and methods To investigate possible genes linked to this disorder, 12 microsatellite markers were selected. They were used in 107 families with MetS and low HDL-C to analyse relevant association and linkage signals. Result Family-based association tests under the biallelic mode gave many positive association signals. Higher association – after correction for multiple testing – was found to be linked with marker D8S1743 and D11S1304 (P

The precise transcriptional regulation of gene expression is essential for vertebrate development, but the role of posttranscriptional regulatory mechanisms is less clear. Cytoplasmic RNA granules (RGs) function in the posttranscriptional control of gene expression, but the extent of RG involvement in organogenesis is unknown. We describe two human cases of pediatric cataract with loss-of-function mutations in TDRD7 and demonstrate that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins (RNPs). TDRD7 coimmunoprecipitates with specific lens messenger RNAs (mRNAs) and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function. These findings demonstrate a role for RGs in vertebrate organogenesis.

Different variant frequencies may lead to different frequencies of the same variants in individuals with drugs resistance and disease susceptibility at the population level. In this study, the allele frequency of three STRs loci including D 11 S 1304, D11S1998, and D11S934 was analyzed on a representative sample of 563 individuals from the capital city of Tehran. The sample included four different ethnic groups. In this sample, 130 individuals were affected with metabolic syndrome (Mets). Calculated parameters on the whole sample were: allele frequency, polymorphic information content values, observed and expected heterozygosity, discrimination power, matching probability, power of discrimination, power of exclusion, and paternity index. For all markers, no significant deviation from Hardy-Weinberg equilibrium was found in observed allele frequencies except D11S1998. There were no significant differences in the allele frequencies in short, medium and long alleles between the metabolic affected subjects and controls. The most significant findings of this study report allele frequency of some STRs on chromosome 11 for the first time in Iran and the observed differences between subjects affected with Mets as opposed to subjects in the control group.

Homozygous beta-thalassemia is a common genetic disorder in the Arabian Peninsula and an important cause of morbidity in Kuwait. The anemia is so severe that chronic blood transfusions, and the resulting iron overload, cause a shift in immunoregulatory balances and a deficiency in zinc. It was reported that individual immunological profile of CD8+ T-lymphocytes may have a modifying effect on the severity of iron overload in HFE homozygous hemochromatosis patients, with low numbers being negatively correlated with the total amount of body iron stores. This has not been tested in thalassemia major patients. This study was designed to utilize flow cytometric immunophenotyping to characterize effects of regular blood transfusion, and high serum ferritin levels because of irregular use of iron chelation therapy on T lymphocytes (CD2, CD3, CD4 and CD8), B lymphocytes (CD19) and natural killer cells (CD56) and zinc levels in the blood of patients with thalassemia major (n = 49) and healthy normal controls (n = 60) in Kuwait. None of the patients had active infections. T-cell markers' percentage levels were comparable between patients and controls (P > 0.05), while B cell marker (CD19) was significantly higher in patients (P = 0.007). Patients had lower percentage levels of CD56 cells (P = 0.007) and normal serum zinc. All patients had high serum ferritin levels with no significant correlation to CD8+ T lymphocytes (P > 0.05). High iron stores did not have an effect on T lymphocytes' profile, with normal zinc levels perhaps related to non compliance with chelation therapy. The high B cell marker may be indicative of stimulation of antibody producing cells as a result of regular blood transfusions.

Introduction: Patients with thalassemia major often present with a hypercoagulable state, the pathogenesis of which is still not understood. Materials and Methods: This study evaluates the risk factors for hypercoagulability in 50 β-thalassemia major patients and 50 healthy controls. Fasting total homocysteine, protein C (PC), protein S (PS), antithrombin (AT), activated protein C resistance (APCR) and lupus anticoagulant (LA) were assessed. MTHFR C677T mutation was determined. Results: Significant reductions in PC, PS and AT were noted in patients. Only 4% of the patients had hyperhomocysteinemia. Thirty-two percent of the patients were heterozygous and 4% were homozygous for MTHFR C677T mutation. Conclusion: The natural coagulation inhibitors PC, PS and AT were significantly reduced in patients with β-thalassemia major and were thus important risk factors for the hypercoagulable state, but hyperhomocysteinemia and MTHFR mutation do not seem to be significant risk factors for thromboembolic events.

Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. Materials andMethod: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. Result: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A–123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct sequencing revealed it was a heterozygous missense mutation G564T (Trp117Cys). Tracking the mutation in the family pedigree showed its origin from the Persian side. Conclusion: This is a second missense G564T mutation in another VHL patient from Kuwait that will help expand our knowledge of the VHL gene mutation spectrum in this region of the world.

Objectives: This study aimed at determining the effects of cigarette smoking based on gender, on several hematological parameters and von Willebrand factor protein in the asymptomatic Arab population of Kuwait. Subjects and Methods: Ninety-two subjects participated in this study: 55 males (31 smokers and 24 nonsmokers) and 37 females (18 smokers and 19 nonsmokers). Complete blood count results were obtained using Beckman Coulter Hematology Analyzer. Von Willebrand factor functional activity was determined using an enzyme-linked immunoassay-based test in which anti-von Willebrand factor IgG monoclonal antibody was used that recognizes a functional epitope of the protein. The coagulation profile was obtained using ACL® 9000 coagulation analyzer. Results: Male smokers had significantly higher levels of white blood cell count (p = 0.03) and von Willebrand factor protein levels (p = 0.029), and a significantly shorter thrombin time (p = 0.019) than nonsmokers. Smoking did not appear to affect any of the parameters analyzed in females as no significant difference was found between smokers and nonsmokers (p > 0.05). Conclusion: Our results showed that smoking affected white blood cell count and von Willebrand factor levels in males and not in females, and as such could be potential markers for smoking-induced endothelial damage in asymptomatic Arab male smokers.

Objective: To examine the concordance between lifestyle practices and beliefs of people living in Kuwait, and between their lifestyle practices and established evidence-informed recommendations for health. Subjects and Methods: A cross-sectional interview questionnaire study was conducted using a convenience sample of 100 adults living in Kuwait (age range 19-75 years). The interview included sections on demographics, and lifestyle-related practices and beliefs related to smoking, diet/nutrition, physical activity/exercise, sleep, and stress. Diet/nutrition and physical activity/exercise benchmarks were based on international standards. Analyses included descriptive statistics and the χ2 test. Results: Beliefs about the importance of nutrition in lifestyle-related conditions were limited, and this was apparent in participants' dietary habits, e.g., low consumption of fruit/vegetables and multigrains: 16 (16%) and 9 (9%) met the recommended guidelines, respectively. Ninety-nine (99%) believed physical activity/exercise affects health overall, and 44 (44%) exercised regularly. Of the sample of 100, 20 (20%) exercised in accordance with evidence-based recommendations for maximal health. Compared with beliefs about other lifestyle-related behaviors/attributes, respondents believed nutrition contributed more than stress to heart disease, cancer, and stroke, and stress contributed more than nutrition to hypertension and diabetes. Conclusion: In this study, our findings showed a discrepancy between lifestyle-related practices and beliefs, and between each of these and evidence-based recommendations for maximal health, i.e., not smoking, several servings of fruit and vegetables and whole-grain foods daily, healthy weight, restorative sleep, and low-to-moderate stress levels.

Background: The human adenovirus-36 (Adv36) has been associated with obesity and lipid disorders in some countries. The primary dyslipidemia related to obesity is characterized by increased TG, decreased HDL levels and abnormal LDL composition. Childhood obesity is a major public health problem in most developing countries. Objectives: The aim of this study was to investigate the association between Adv36 and lipid disorders in Tehranian youth. Patients and Methods: In a cross-section/observational study, anthropometric, blood pressure and biochemical measurements were examined in 54 youth, aged below 19 years, selected randomly from participants of Tehran Lipid and Glucose Study (TLGS) of Iran. Human Adv36 antibody of serum was determined using ELISA method. Results: Of 54 youth, with a mean age of 14.78 ± 2.62 years, 85.2% were Adv36 seropositive (N = 46) and 14.8% were seronegative (N = 8). Subjects with Adv36 seropositive had higher mean of age, weight, TC, LDL-C, TG and SBP and lower level of HDL-C, waist, FBS and DBP. The unadjusted OR for elevated TG increased in participants who were Adv36 seropositive (OR 3.062, 95% CI: 0.344-27.293). Although the unadjusted OR for other lipid variables, such as elevated TC and LDL-C or decreased HDL-C, tended to increase in participants who were Adv36 seropositive (OR 1.028, 95% CI: 0.996 - 1.060; OR 1.057, 95% CI: 0.107 - 10.481; OR 1.125, 95% CI: 0.238 - 5.325, respectively), the results were not significant. Conclusions: It seems that seropositive Adv36 has a strong association with lipid disorders, especially elevated TG level in Tehranian children and adolescent.

Iron deficiency anemia (IDA) and thalassemia minor are two of the most common causes of microcytic anemias worldwide. Because of similar red blood cell count parameters and blood picture, it was imperative to develop other measures that would differentially and correctly diagnose these two anemias. Several mathematical formulas and simple RBC indices have been introduced as simple, fast and inexpensive means of providing differential diagnosis for IDA and thalassemia minor. The Objective of this study was to apply and compare nine well-documented discriminant functions on a population of 153 confirmed cases of microcytic anemias (IDA n = 56, beta-thalassemia minor n = 47 and alpha-thalassemia n = 50) and to measure validity using Youden's Index. The results show that England and Fraser (E & F) Index had the highest Youden's Index value (98.2) in correctly differentiating between IDA and alpha- and beta-thalassemia minor, while Shine and Lal Index was found ineffective in differentiating between microcytic anemias in our population. E & F Index showed with great sensitivity and specificity to be the best discriminant function to differentiate between IDA and thalassemia minor cases.

Purpose To report the spectrum of the CYP1B1 mutation in Kuwaiti patients with primary congenital glaucoma (PCG). Design Clinical diagnosis of PCG and laboratory based experimental study. Methods Polymerase chain reaction-restriction polymorphism length fragment (PCR-RPLF) and direct sequencing of exon 2 and the coding region of exon 3 of CYP1B1 gene were the methods used for screening 17 PCG patients, their families, and 105 health individuals from the same ethnicity. Results Four different mutations were detected in CYP1B1 in 70.6% of the screened patients. The most common one (47%) was homozygote Gly61Glu mutation, previously described in Saudi Arabia, Turkey, and Morocco; all patients were products of consanguineous marriages. The second common mutation was a novel missense (Ala388Thr) mutation found in three patients (17.6%) as compound heterozygote with Arg368His in one patient, and with Gly61Glu in another one while the second mutation in third patient was not detected in the CYP1B1 gene. One patient (5.8%) was homozygote for Cyt280X mutation previously reported in only one Japanese family. In addition to these mutations, a novel Val422Gly polymorphic site was found in three of the PCG patients and in 18 of the 210 tested chromosomes of healthy volunteers. Conclusions The CYP1B1 mutation spectrum of Kuwaiti PCG patients is similar to that detected in the neighboring countries. No clear genotype-phenotype correlation detected in patients showed different types of CYP1B1 mutation.

Objectives: To compare the performance of SEDIsystemTM, a fully automated analyzer for the measurement of the erythrocyte sedimentation rate (ESR), with the manual Westergren method. Materials and Methods: Both methods were applied to 150 randomly selected subjects. The linear regression and Bland and Altman data analysis methods were used to measure the agreement between the automated and manual methods. Results: The regression analysis showed a good correlation between the two methods (r = 0.91). The Bland and Altman data analysis showed no systematic bias (95% confidence interval for mean difference); however, limits of agreement were between 11.52 and –37.88. This indicates that ESR values measured by the SEDIsystem may be 11.52 mm/h above or 37.88 mm/h below the reference method. A greater scatter of data was also observed with abnormally high (>25 mm/h) ESR results (mean of difference = –21.4 and limits of agreement = –45.2 and 2.26) compared with normal (Conclusion: The Bland and Altman statistical analysis showed a wide degree of scatter between results obtained by the two ESR techniques that was not clearly demonstrated using the linear regression analysis. The automated system was found to underestimate ESR with the Bland and Altman statistical analysis, and therefore a correction factor is recommended.

Background: DNA variations within the AngiotensinConverting Enzyme (ACE) gene have been shown to be involved in the aetiology of several common diseases and the therapeutic response. Methods: This study reports a comparison of haplotype analysis of five SNPs in the ACE gene region using a sample of 100 healthy subjects derived from five different populations (Tunisian, Iranian, Kuwaiti, Bahraini and Indian). Results: Strong linkage disequilibrium was found among all SNPs studied for all populations. Two SNPs (rs1800764 and rs4340) were identified as key SNPs for all populations. Conclusions: These SNPs will be valuable for future effective association studies of the ACE gene polymorphisms in Arab and Asian populations.

Background: Variation in drug resistance and susceptibility to various diseases may be related to difference in allele frequencies of the variants at the population level. Objectives: The present study aimed to investigate the allele frequencies of five short tandem repeats (STR) loci in two different chromosomes of candidates from Tehran lipid and glucose study. Materials and Methods: For this study, a representative sample of 563 individuals (130 affected by metabolic syndrome) from Tehran, including four different ethnic groups of Iran, was selected. Five STRs including D12S1632, D12S329, D12S96, D16S3096 and D16S2624 were analyzed using the fragment analysis method. Allele frequency, polymorphism information content (PIC) values, observed and expected heterozygosity, discrimination power, matching probability, power of discrimination, power of exclusion and paternity index were calculated for the whole sample. Results: There was no significant deviation in allelic frequencies from Hardy-Weinberg equilibrium for all the studied markers except for D12S1632 and D12S329. The long alleles in D12S329 were significantly more frequent in patients with metabolic syndrome (P < 0.05). Conclusions: This study revealed allele frequency of some STRs on chromosome 12 and 16 for the first time in Iran, and indicated differences between subjects with metabolic syndrome and subjects in the control group.

We analyzed the Y-chromosome haplogroup diversity in the Kuwaiti population to gain a more complete overview of its genetic landscape.A sample of 117 males from the Kuwaiti population was studied through the analysis of 22 Y-SNPs. The results were then interpreted in conjunction with those of other populations from the Middle East, South Asia, North and East Africa, and East Europe.The analyzed markers allowed the discrimination of 19 different haplogroups with a diversity of 0.7713. J-M304 was the most frequent haplogroup in the Kuwaiti population (55.5%) followed by E-M96 (18%). They revealed a genetic homogeneity between the Kuwaiti population and those of the Middle East (FST = 6.1%, P-value 0.0001), although a significant correlation between genetic and geographic distances was found (r = 0.41, P-value = 0.009). Moreover, the nonsignificant pairwise FST genetic distances between the Kuwait population on the one hand and the Arabs of Iran and those of Sudan on the other, corroborate the hypothesis of bidirectional gene flow between Arabia and both Iran and Sudan.Overall, we have revealed that the Kuwaiti population has experienced significant gene flow from neighboring populations like Saudi Arabia, Iran, and East Africa. Therefore, we have confirmed that the population of Kuwait is genetically coextensive with those of the Middle East.

The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. Three reactions are involved in methylenetetrahydrofolate recycling: Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). Malarial bifunctional DHFR-TS is a well-studied, important target of established drugs such as pyrimethamine and cycloguanil. In sharp contrast, malarial SHMT remains largely uncharacterized. In the present study, a Plasmodium falciparum SHMT coding region was characterized. It had 1603 bp including two introns near the 5'-end of the gene: one 118 bp intron immediately after the start methionine and a 159 bp intron after an additional 34 amino acids. The three exons together coded for a 442 amino acid protein with 38-47% identity to SHMT sequences from other species. Expression of malarial SHMT coding sequence (minus the introns) into glyA mutants of Escherichia coli relieved glycine auxotrophy and permitted direct assay of SHMT catalytic activity in bacterial cell lysates. This is the first SHMT cloned and expressed from a protozoan parasite. The molecular tools developed in this study will be useful for developing potential antimalarials directed at SHMT.

Summary Malaria infects over 200 million individuals and kills 2 million young children every year. Understanding the biology of malarial parasites will be facilitated by DNA microarray technology, which can track global changes in gene expression under different physiological conditions. However, genomes of Plasmodium sp. (and many other important pathogenic organisms) remain to be fully sequenced so, currently, it is not possible to construct gene-specific microarrays representing complete malarial genomes. In this study, 3648 random inserts from a Plasmodium falciparum mung bean nuclease genomic library were used to construct a shotgun DNA microarray. Through differential hybridization and sequencing of relevant clones, large differences in gene expression were identified between the blood stage trophozoite form of the malarial parasite and the sexual stage gametocyte form. The present study lengthens our list of stage-specific transcripts in malaria by at least an order of magnitude above all previous studies combined. The results offer an unprecedented number of leads for developing transmission blocking agents and for developing vaccines directed at blood stage antigens. A significant fraction of the stage-selective transcripts had no sequence homologues in the current genome data bases, thereby underscoring the importance of the shotgun approach. The malarial shotgun microarray will be useful for unravelling additional important aspects of malaria biology and the general approach may be applied to any organism, regardless of how much of its genome is sequenced.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disorder of the central nervous system.To explore the genetic basis of three nitric oxide synthase (NOS) genes: NOS1, NOS2A and NOS3, with susceptibility to MS.A total of 122 MS patients and 118 healthy controls screened for NOS1 (rs2682826, rs41279104), NOS2A (CCTTT)n/(TAAA)n and NOS3 (rs1800783, rs1800779, rs2070744, 27bpVNTR) markers, using TaqMan®SNP Genotyping Assays and fragment analysis were enrolled in this study. QRT-PCR and ELISA were used to analyse the expression of NOS3 mRNA and Nitric Oxide (NO) levels.Two NOS3 markers were associated with susceptibility to MS and early disease development. The NOS3 rs1800779 G-allele (p = 0.04) and GG-genotype (p = 0.02) showed association with susceptibility to MS. Short NOS2 (CCTTT)n (p = 0.03) and short/long repeat (p = 0.04) genotypes also showed associations with MS. These associations were intensified by sub-division of patients into Kuwaiti Arabs and Persians (p 0.05). The NOS3-27 bp-VNTR a-allele was associated with early MS disease onset ≤26 years (p = 0.04). The NOS3-27 bp-VNTR a/b-genotype resulted in 23% lower NO production and the NOS3-rs1800779 AA-genotype resulted in lower NOS3 expression. Haplotypes obtained from NOS2A and NOS3 showed increased susceptibility to MS. NOS1 showed no significant association with MS.This study provides evidence for the association between selected NOS2 and NOS3 markers and MS susceptibility.

Present study was aimed to explore the effect of (TA)n UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls) using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7). (TA)6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p

Seventeen Y-chromosomal Short Tandem Repeats (Y-STR) included in the AmpF l STR Y-filer PCR Amplification kit (Applied Biosystems) (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4) were genotyped in a population sample of 176 unrelated males from western Libya (Tripoli region). A total of 142 different haplotypes were found, 124 being unique. Haplotype diversity was 0.9950. Both R ST pairwise analyses and multidimensional scaling plot show a close genetic relationship between Tripoli and North African populations.

Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. The study of such causal mutations is a central focus of cancer biology for two reasons; first is to reveal the molecular mechanisms of tumorigenesis, second is to provide insight in the development of novel therapeutic and diagnostic approaches. Although hundreds of genes are known to be mutated in cancers our understanding of mutational events in cancer cells remains incomplete (Futreal PA et al, 2004). This however has widely opened the field of cancer genomics studies which aims to provide new insights into the molecular mechanisms that lead to tumorigenesis.

Purpose To explore the disease locus and causative mutation for autosomal dominant congenital cataracts (ADCC) in a Kuwaiti family. There were seven affected and three unaffected subjects in the family. Methods Whole-genome linkage analysis was performed using Gene Chip Human Mapping 250 K Arrays to identify regions of linkage. Potential genes within this region were cloned and sequenced to identify the disease-causing mutation. Results The highest logarithm of odds score (1.5) region 2q34–36.1, spanning the crystallin beta A2 (CRYBA2) gene, showed no sequence changes. Thus, the second highest logarithm of odds score (1.49) region, 2q33–37, spanning the gamma crystalline gene cluster (CRYG), was considered. Sequencing of the CRYGA, B, C, and D genes revealed two novel heterozygous deletions and one trinucleotide polymorphism in the CRYGB gene. These mutations included a heterozygous g.67delG, intron 1 deletion in four of the affected family members with lamellar cataracts and a heterozygous g.167delC, exon 2 deletion inherited from the Egyptian grandmother by her granddaughter, resulting in anterior polar cataracts. Another patient with complete cataracts was a compound heterozygote with both of the above-mentioned mutations. In addition, the novel trinucleotide polymorphism g.20–22 GGT>AAA was detected in three of the family members. Conclusions We report the linkage of ADCC to chromosome 2q33–37, which spans the CRYGB gene. This study is the first to report complex heterogeneous mutations in the CRYGB gene resulting in ADCC with three distinct phenotypes (lamellar, anterior polar, and complete cataracts) in the same family.

High-density lipoprotein cholesterol (HDL-C) levels are low in Iranians. Low HDL-C is the most frequent phenotype in metabolic syndrome (MetS) among the Iranian population (32%). This has been claimed to be related to genetic factors.To investigate possible genes linked to this disorder, 12 microsatellite markers were selected. They were used in 107 families with MetS and low HDL-C to analyse relevant association and linkage signals.Family-based association tests under the biallelic mode gave many positive association signals. Higher association - after correction for multiple testing - was found to be linked with marker D8S1743 and D11S1304 (P0·003). The obtained results suggested evidence for association with regions on chromosome 8, 11 and to a lesser degree on chromosome 16. Nonparametric linkage analysis performed by Merlin software gave no significant correlation for any of the chromosomal regions. By considering only families with positive Nonparametric Logarithm of odds (LOD) scores, higher association can clearly be visible with D16S3096 and D11S934.These results suggest that 8q22-24; 11q23-25 and 16q23-24 regions are very likely to contain genes that control HDL-C level in Iranian families with metabolic syndrome.