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Boron possesses widespread properties in biochemistry and nutrition. Acute supplementation with 11.6 mg of boron resulted in a significant increase in plasma boron concentration. Given such a fast bioavailability, the objective was to determine whether acute (hourly or daily), and weekly supplementation could have any significant biological effects on the steroid hormones and further on some inflammatory biomarkers. Eight healthy male volunteers attended the laboratory on three occasions (days 0, 1 and 7). On the first day (day 0), a blood sample collection at 8.00 A.M was followed by ingestion of placebo with the breakfast. On the next day (supplementation-day 1), similar procedure was followed by ingestion of a capsule containing 10mg of boron. On both occasions blood was collected every 2h for the next 6h. Subjects were requested to consume a capsule of 10mg boron every day with their breakfast, and on the day 7, the blood collection was carried out at 8.00 A.M, again. Boron in plasma increased significantly following hours and weekly consumption. Six hours supplementation showed a significant decrease on sex hormone binding globulin (SHBG), high sensitive CRP (hsCRP) and TNF-α level. After one week (in samples taken at 8.00 A.M, only), the mean plasma free testosterone increased and the mean plasma estradiol decreased significantly. Dihydrotestosterone, cortisol and vitamin D was elevated. Also, concentrations of all three inflammatory biomarkers decreased after supplementation. Of note, despite decreased proinflammatory cytokines, based on recent clinical data, this must be the first human study report to show an increase level of free testosterone after boron consumption.

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.

The prevalence of cardiovascular risk factors, especially low level of high density lipoprotein cholesterol (HDL-C), is very high in Iran. The associations of apolipoprotein E (Apo E) polymorphism with lipid profile, especially high density lipoprotein (HDL) subfractions, were examined in Iranian population. A cross-sectional study of 1030 subjects (452 men and 578 women) from the Tehran Lipid and Glucose Study (TLGS) was performed. Serum triacylglycerol, cholesterol, FBS, HDL-C levels and its subfractions, Apo B and Apo A 1 were determined and body mass index and blood pressure were measured. A segment of the mentioned gene was amplified by PCR and the polymorphisms were revealed by RFLP using HhaI restriction enzyme. Allele frequencies obtained for APOE * 2, APOE * 3, and APOE * 4 were 5.77, 85.92, and 8.3%, respectively. The presence of the e2 allele was significantly associated with increased serum HDL-C levels and its subfractions both in men and women except HDL3 in men. The LDL/HDL ratio was significantly lower in female. The relations were significant even after adjustment for age, sex, and BMI but hypertension, smoking, and diabetes status decreased the effect of Apo E2 on HDL-C and HDL subfractions. The observed genotype and allele frequencies were similar to those reported for other Caucasians samples. Apo E2 increased the level of HDL-C, HDL subfractions, and decreased the LDL/HDL ratio. These findings highlight the important effect of variation in this gene on lipid levels.

In this study the association between beta3-adrenoceptor gene polymorphism and serum concentration of leptin with body mass index (BMI) is investigated. Using subjects in the Tehran Lipid and Glucose Study, genotyping of the Trp64Arg polymorphism of the beta3-adrenoreceptor gene was performed using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used and the association with obesity was investigated. At total of 197 men and 204 women were divided into four groups (BMI

Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery.This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs.Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.

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.

1Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran 2Department of Public Health, Statistics and Epidemiology, Tabriz University of Medical Sciences, Tabriz, IR Iran 3Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, Netherlands 4Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran 5Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran

Approximately one-third of diabetic patients develop evidence of nephropathy. Pathogenesis of diabetic nephropathy (DN) remains unclear; however, some genetic and metabolic risk factors have been determined for the development and progression of DN. In the recent genetic studies, polymorphism of apolipoprotein E (ApoE) gene has been reported as a risk factor for the development of DN; however, the results are inconsistent. The aim of the present study was to evaluate the association between ApoE polymorphism and nephropathy in Iranian patient with type 2 diabetes. A total of 197 patients with type 2 diabetes in two groups with and without nephropathy (n = 99 and n = 98, respectively) participated in this case–control study. ApoE genotype was determined by restriction fragment length polymorphism analysis. Biochemical factors of all patients were measured. The frequency of Apo ε4 allele was significantly (P

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.

Background: Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) gene is associated with interindividual variance in bone mineral density (BMD). Objectives: The aim of this study was to assess the association between BMD and the VDR gene polymorphisms. Patients and Methods: A total of 233 women including 124 premenopausal and 109 postmenopausal women, who were older than 40 years old, were randomly selected from the participants of Tehran Lipid and Glucose Study (TLGS). Serum 25 (OH) vitamin D, calcium, and phosphorus levels were measured and body mass index (BMI), BMD of femoral neck, total femoral, trochanteric, and lumbar spine bones were calculated. The polymerase chain reaction (PCR) was used to determine the Bsm1 and Tru91 polymorphisms of VDR gene. Results: According to PCR results, Bb genotype frequencies in premenopausal and postmenopausal woman were 39.5% and 31.2%, respectively, and Tt genotype frequencies were 41.9% and 33%, respectively. Moreover, b and T alleles were more frequent in these women, with a frequency of 0.57% and 0.18%, respectively. In premenopausal subjects, the mean BMD at all sites were higher in bb group than in the BB group (P < 0.05). After adjustment for age, BMI, and serum 25 (OH) D, the bb group had lower BMD at all these sites in postmenopausal women; however, the difference was insignificant. There was no association between Tru91 polymorphism and BMD in premenopausal and postmenopausal women. Conclusions: It seems that there is a possible interaction between premenopausal status and the Bsm1 polymorphism of VDR gene polymorphism and the BMD levels in these regions.

Patients and Methods: This cross-sectional family-based study was conducted on 769 TLGS families in Iran. All families with two biological parents, at least one offspring (nuclear family) and at least two overweight or obese members were eligible for this study. Participants, who lacked the complete family and demographic variables were excluded. Consequently, 529 two-generation nuclear families (1066 parents and 1394 offspring) remained. Obesity-related variables, including waist circumference (WC), waist to hip ratio (WHR), body mass index (BMI), resting energy expenditure (REE), and body size (BS) were determined. Variance component method was used to estimate the age and sex adjusted heritability for obesity-related variables using SOLAR software. Results: Recruited families consisted of 2460 individuals (493 fathers, 573 mothers, 720 sons, and 674 daughters). Parents and offspring were aged 45.7 ± 10.2 and 18.4 ± 9.7 years respectively. The age and sex adjusted heritability for all obesity-related variables were significant (P < 0.0001) and varied from 0.21 (hip) to 0.51 (BS). The heritability for body size considerably surpasses the heritabilities, which were estimated in this study. Conclusions: This study indicates that Tehran families are genetically predisposed to obesity; although, inappropriate lifestyle may interfere with genetic patterns.

The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transportation. The aim of this study was to assess the association between exon1 (G → A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population.This cross-sectional study included 774 adults (322 males and 452 females) aged 20-70 years who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism, via Alu restriction enzyme.Minor allele frequency for SR-BI polymorphism in the selected population was 0.159. Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Association between (G → A) SR-BI polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was significant only after adjustment for age as a potential covariate (p = 0.046, 0.041, respectively); however, the results did not improve after adjustment for sex.The result of this study confirms the role of age as a potential confounder which could modify the association between the SR-BI single nucleotide polymorphism and HDL-C level.

BACKGROUND The study was conducted to obtain the frequency of the hepatic lipase C-514T polymorphism and evaluate its relation with serum HDL cholesterol levels in Tehran. METHODS A segment of the gene mentioned was amplified by polymerase chain reaction in 545 people and the restriction fragment length polymorphism revealed. RESULTS The T allele frequency was 0.154. No significant relationship between HDL cholesterol levels and C-514T polymorphism was found even after adjusting for age, body mass index and blood pressure. CONCLUSION The frequency of the polymorphism is similar to other Caucasian populations and no significant relationship exists between the non-CC genotype of the gene and a higher serum HDL cholesterol concentration.

Among the most common lipid abnormalities, a low level of high-density lipoprotein-cholesterol (HDL‑C) is one of the first risk factors identified for coronary heart disease. Lecithin cholesterol acyltransferase (LCAT) has a pivotal role in the formation and maturation of HDL-C and in reverse cholesterol transport. To identify genetic loci associated with low HDL-C in a population-based cohort in Tehran, the promoter, coding regions and exon/intron boundaries of LCAT were amplified and sequenced in consecutive individuals (n=150) who had extremely low or high HDL-C levels but no other major lipid abnormalities. A total of 14 single-nucleotide polymorphisms (SNPs) were identified, of which 10 were found to be novel; the L393L, S232T and 16:67977696 C>A polymorphisms have been previously reported in the SNP Database (as rs5923, rs4986970 and rs11860115, respectively) and the non-synonymous R47M mutation has been reported in the Catalogue of Somatic Mutations in Cancer (COSM972635). Three of the SNPs identified in the present study (position 6,531 in exon 5, position 6,696 in exon 5 and position 5,151 in exon 1) led to an amino acid substitution. The most common variants were L393L (4886C/T) in exon 6 and Q177E, a novel mutation, in exon 5, and the prevalence of the heterozygous genotype of these two SNPs was significantly higher in the low HDL-C groups. Univariate conditional logistic regression odds ratios (ORs) were nominally significant for Q177E (OR, 5.64; P=0.02; 95% confidence interval, 1.2‑26.2). However, this finding was attenuated following adjustment for confounders. Further studies using a larger sample size may enhance the determination of the role of these SNPs.

Aims Polycystic ovary syndrome (PCOS), a common female endocrine disorder, represents a wide range of clinical manifestations and disease severity. Recent studies suggest an association between gene variants involved in vitamin D metabolism and common metabolic disturbances in PCOS. We aimed to examine the association of vitamin D receptor (VDR) gene variant with PCOS susceptibility and the severity of disease phenotype. Methods All participants, including 260 PCOS women (cases) and 221 normoovulatory women (controls), were recruited from a reproductive endocrinology clinic. Cases were divided into the severe and mild PCOS phenotype groups, based on their clinical and paraclinical features. An adenosine to guanine single nucleotide polymorphism of VDR gene (rs757343) was genotyped using the PCR–RFLP method. Results Distributions of genotypes and alleles did not differ between cases and controls, indicating that this SNP is not associated with increased risk for PCOS. However, this SNP was found to be associated with the severity of the PCOS phenotype. In particular, presence of the A allele is associated with a 74% increased risk of severe phenotype development (OR, 1.74; 95% CI, 1.07–2.82). Conclusion The genetic variant of the VDR was found to have an association with severity of clinical features of PCOS, but none with disease risk.

Considering the key role played by the apolipoprotein E (Apo E) gene in the regulation of lipid metabolism and obesity, the current study has evaluate the association between abdominal obesity and Apo E gene polymorphism in a population of Tehran.A cross-sectional study was performed on 345 men and 498 women, aged 19-86 years, selected from among participants of the Tehran Lipid and Glucose Study. The RFLP-PCR technique was employed to investigate polymorphism in the gene fragments. Based on the national survey of risk factors for non-communicable diseases of Iran, waist circumference (WC) cut off was set at 89 cm for men and 91 cm for women. The risk effect of obesity related variables and lipid profiles in two groups of WC were examined by logistic regression. For body mass index (BMI), waist to hip ratio (WHR), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and blood pressure (BP), the standard risk cut-offs were applied.Frequencies of E2, E3, and E4 alleles were 9.7, 73, and 14.6%, respectively. The presence of the E3 allele was significantly associated with higher TG level in subjects with high WC, while, the presence of E4 allele decreased the plasma HDL-C (E2:52.1±13.1 vs., E3:48.9±11.2 vs., E4:44.6±10.6 mg/dl, p0.05), HDL-C2 (E2:20.4±9.2 vs., E3:19.1±8.8 vs., E4:16.3±7.9 mg/dl, p0.05), and HDL-C3 (E2:32.1±7.4 vs., E3:30.3±6.2 vs., E4:28.3±6.1 mg/dl, p0.05) in normal WC subjects. The presence of the E3 carrier increased the risk of having higher plasma TG, compared with the E2 carrier (95% CI OR=1.91, 1.02-3.57; p=0.04).According to the results of this study, the E3 carrier, caused an approximately 90% increase in the levels of TG in the group with abdominal obesity.

Introduction Thyroid peroxidase (TPO) gene variations are one cause of thyroid autoimmune diseases. The aim of this study was to examine the association between the T1936C, T2229C and A2257C polymorphisms of the TPO gene and Anti-TPO level. Materials and methods In this case–control study, 188 individuals (86 males and 102 females), aged 20–80 years, were randomly selected from among the Tehran Lipid and Glucose Study (TLGS) population. A2257C and T2229C SNPs were detected with RFLP by use of BsrI and Eco57I as the restriction enzymes respectively, while the T1936C SNP was determined with ARMS-PCR. Results In the presence of the C allele of T1936C, Anti-TPO level was significantly increased (CC: 238 ± 43.3, CT: 47.7 ± 15.9, TT: 74.1 ± 11.3 IU/L p = 0.002); however, this association was attenuated after adjustment for sex and age (p = 0.059). No significant difference, before and after adjustment, was found in Anti-TPO level in the presence of T2229C SNP (CC: 129.1 ± 24.5, CT: 43.5 ± 12.6, TT: 126.5 ± 13.8 IU/L p = 0.196). The association between A2257C and Anti-TPO level was only significant after adjustment for potential confounders (p = 0.007). The association between ATC and CTT haplotypes and Anti-TPO level was significant (p = 0.023, 0.021 respectively), the association between CTT and Anti-TPO concentration was also significant after adjustment for sex (p = 0.014). Conclusion The results of the present study confirmed the association between TPO gene polymorphisms and Anti-TPO level in the Tehranian population.

Introduction Different variants of haplotype frequencies may lead to various frequencies of the same variants in individuals with drug resistance and disease susceptibility at the population level. Materials and methods In this study, the haplotype frequencies of 4 STR loci including the D8S1132, D8S1779, D8S514 and D8S1743, and 3 STR loci including D11S1304, D11S1998 and D11S934 were investigated in 563 individuals of four Iranian ethnic groups in the capital city of Iran, Tehran. One hundred thirty subjects had the metabolic syndrome. Haplotype frequencies of all markers were calculated. Results There were significant differences in the haplotype frequencies in short and long alleles between the metabolic affected subjects and controls. In addition, haplotype frequencies were significant in the four ethnic groups in both chromosomes 8 and 11. Conclusion Our findings show a relation between the short allele of D8S1743 in all related haplotype frequencies of subjects with metabolic syndrome. These findings may require more studies of some candidate genes, including the lipoprotein lipase gene, in this chromosomal region.

Background: High temperature and long heating time can be considered the main drawbacks of the conventional digestion methods of urinary iodine determination. The aim of this study was to assess the usefulness of a microwave for digestion and decomposition of urine interfering substances. It may help for shortening the time and increasing the safety of the method. Methods: In this study, two digestion methods were tested on urine samples. Random urine samples were processed by conventional electrical heat as well as new microwave digestion methods. The urine samples were digested using the two methods mentioned, and then urinary iodine was determined using a colorimetric reaction according to the Sandell-Kolthoff reaction. In order to increase speed and precision of the test, a microplate ELISA reader was used. Sensitivity, precision, and comparison of the results were assessed in both of the methods. Results: In the case of microwave digestion, only a 10-min period was needed for complete digestion of urine samples. The precision and recovery of the new digestion step was acceptable. Furthermore, comparison of final results of iodine content obtained using the microwave and conventional method showed good correlation. Conclusions: These results show that a microwave method for urine digestion is advantageous due to its safety and ease of use, and quick preparation of urine samples to eliminate interfering substances and release iodine. Thus, it can replace the conventional electrical heat digestion method.

Iodine deficiency leads to deficiency of thyroid hormones, which causes mental retardation in infant. Laboratory confirmation is important in its diagnosis. The major problems associated with the existing methods for iodine determination in milk samples are: 1) nonsafe alkaline solution; 2) harsh thermal condition; and 3) extra time required to complete various steps. In this study, a simple and rapid colorimetric method was investigated, which used acid digestion in combination with a rapid microplate reading format method to determine the total iodine content in milk. Sample digestion was done on 50 µL milk in metavanadate/perchloric, at 230°C for 10 min. After digestion, iodine determination was based on the Sandell‐Kolthoff reaction. The reaction results were read in 96‐well microplates by an enzyme‐linked immunosorbent assay (ELISA) reader. The determination range of the assay was between 2 and 40 µg/dL. The within‐run coefficient of variation percent in three levels (3, 12, and 36 µg/dL) ranged from 6.7 to 9.3 and between‐run coefficients of variation ranged from 8.6 to 12.3%. The results obtained (n=70) by the optimized method have good correlation with the results of alkaline incineration as a reference method (n=70; r(2)=0.907; y=0.952x+1.77). Recovery tests for accuracy assessment in six levels from 6.2 to 34.2 µg/dL) were between 91.3 and 113%. This method has enabled us to achieve 0.12 µg/dL sensitivity. The results of this study show that a quick acid digestion combined with mild thermal and low sample volume with a quick reading of assay results were the main advantages of the acid digestion and microplate reading format. J. Clin. Lab. Anal. 21:286–292, 2007. © 2007 Wiley‐Liss, Inc.

Through high coverage whole-genome sequencing and imputation of the identified variants into a large fraction of the Icelandic population, we found four independent signals in the low density lipoprotein receptor gene (LDLR) that associate with levels of non-high density lipoprotein cholesterol (non-HDL-C) and coronary artery disease (CAD). Two signals are novel with respect to association with non-HDL-C and are represented by non-coding low frequency variants (between 2–4% frequency), the splice region variant rs72658867-A in intron 14 and rs17248748-T in intron one. These two novel associations were replicated in three additional populations. Both variants lower non-HDL-C levels (rs72658867-A, non-HDL-C effect = -0.44 mmol/l, P adj = 1.1 × 10−80 and rs17248748-T, non-HDL-C effect = -0.13 mmol/l, P adj = 1.3 × 10−12) and confer protection against CAD (rs72658867-A, OR = 0.76 and P adj = 2.7 × 10−8 and rs17248748-T, OR = 0.92 and P adj = 0.022). The LDLR splice region variant, rs72658867-A, located at position +5 in intron 14 (NM_000527:c.2140+5G>A), causes retention of intron 14 during transcription and is expected to produce a truncated LDL receptor lacking domains essential for function of the receptor. About half of the transcripts generated from chromosomes carrying rs72658867-A are characterized by this retention of the intron. The same variant also increases LDLR mRNA expression, however, the wild type transcripts do not exceed levels in non-carriers. This demonstrates that sequence variants that disrupt the LDL receptor can lower non-HDL-C and protect against CAD., Author Summary Cholesterol levels in the bloodstream, in particular elevated low-density lipoprotein cholesterol (LDL-C), are strong risk factors for cardiovascular disease, and LDL-C reduction reduces mortality in people at risk. One of the major determinants of plasma LDL-C levels is the low density lipoprotein receptor (LDLR) that acts as a scavenger for cholesterol rich lipoprotein particles. Mutations that disrupt the function of the LDLR or lead to reduction in the number of LDLR usually result in elevated LDL-C in blood. In the current study, we identified, through whole-genome sequencing and imputation into a large fraction of the Icelandic population, four LDLR gene variants that affect non-HDL-C levels (that includes cholesterol in LDL and other pro-atherogenic lipoproteins) and risk of coronary artery disease (CAD). Two variants are known and two are novel. One of them, a splice region variant in intron 14 (rs72658867-A), affects normal splicing and is predicted to generate a truncated LDLR, lacking domains essential for receptor function. Despite this, rs72658867-A lowers non-HDL-C substantially and protects against CAD in the general population, demonstrating that variants that disrupt the LDLR can result in lower cholesterol levels.

Material and Methods: 22 nuclear families (78 persons including 12 patients) with papillary and follicular tumors were selected in a period of six months from Milad hospital. Five microsatellite markers (D19S413, D19S391, D19S916, D19S568, D19S865) on 19p13.2 were selected for genetic analysis. Genomic DNAs was extracted; PCR and polyacrylamide gel electrophoresis method were used for variation detection. Results: The results show that 5.4% of the follicular carcinomas and 17.9% of the papillary carcinomas presented LOH at recognition sites. LOH of Papillary carcinoma detected about 13.9% and follicular carcinoma 7.2% in this study. The frequency of informative cases was not similar for each marker: D19S413 (41.1%)[1], D19S391 (12.5%), D19S916 (10.7%), D19S568 (1.8%) and D19S865 (3.6%). Loss of hetrozygosity in D19S413 predicts the relation between variation in this region and the disease. Discussion: Our findings showed an average of 13.9% LOH in FNMTC cases. Among the five major microsatellites, D19S413 was the most informative for LOH analysis of FNMTC.

Background Low level of high density lipoprotein cholesterol (HDL-C) has high prevalence in the Tehran Lipid and Glucose Study (TLGS) cohort. About 50% of the inter-individual variation in serum HDL-C levels is genetically determined. Polymorphisms in cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) genes have been found to be associated with the metabolism and serum concentration of the HDL-C. Objectives To determine the association between Taq1B polymorphism in CETP gene and -514C/T polymorphism in LIPC gene with serum lipid levels and lipid peroxidation in a subgroup of the TLGS population. Results Serum HDL-C level had significant association with CETP Taq1B polymorphism and B2B2 subjects had the highest HDL-C levels compared to B2B1 and B1B1 genotypes (37.9 vs. 36.9 and 35.3 mg/dl, respectively; P = 0.01). However, carriers of "B1" allele, in comparison to the non carriers (B2B2), had significantly lower levels of TC (200.1 vs. 215.2 mg/dl; P = 0.005), HDL-C (35.8 vs. 37.9 mg/dl; P = 0.009) and malondialdehyde MDA (4.5 vs. 5.0 nmol/mL; P=0.031). Carriers of the "T" allele in -514C/T polymorphism in LIPC gene had higher means of HDL-C than non carriers (37.7 vs. 35.7 mg/dl, P = 0.04). No other association was found between -514C/T polymorphism and any other serum lipids or MDA level. Conclusion This study demonstrates the association between Taq1B and -514C/T polymorphisms in the CETP and LIPC genes with the serum HDL-C levels.

We examined the cholesteryl ester transfer protein (CETP) gene TaqI intron 1 B1/B2 polymorphism and the -629A/C CETP promoter polymorphism in respect to high-density lipoprotein cholesterol (HDL-C) in a healthy Iranian population taken from the Tehran Lipid and Glucose Study (TLGS). The relationship between CETP activity and HDL-C level was also determined along with body mass index, blood pressure and tobacco smoking status. PCR-RFLP used to amplify a segment of the CETP intron 1 TaqI (B2/B1) polymorphism from 1021 individuals and we selected 345 individuals from the lowest, middle and highest HDL-C deciles and investigated the -629A/C polymorphism. We also evaluated the CETP activity of 103 of these individuals, each with at least one homozygous allele. The presence of the TaqI B2 and -629A/C A alleles were significantly associated with increased HDL-C levels (B2B2 = 1.19 ± 0.31 mmolL-1 vs. B1B1 = 1.01 ± 0.2 mmol L-1 for p < 0.001; AA = 1.15 ± 0.41 mmol L-1 vs. CC = 0.95 ± 0.28 mmol L-1 for p < 0.001) and decreased the CETP activity (B1B1 = 67.8 ± 8.9 pmol L-1 vs. B2B2 = 62.6 ± 9.6 pmol L-1 for p < 0.01; CC = 68.6 ± 8.4 pmol L-1 vs. AA = 62.7 ± 9.7 pmol L-1 for p < 0.002). The frequencies were 0.382 for the TaqI B2 allele and 0.462 for the -629A/C A allele, with linkage disequilibrium analysis giving D = 0.0965 and D' = 0.4695. We demonstrated that the TaqI B1 and B2 alleles and the -629A/C A and C alleles were in linkage disequilibrium in our population and that there was a significant association between the B2 and A alleles and high HDL-C levels and low CETP activity. Linkage disequilibrium between the TaqI A and B2 alleles also detected.

Background Diabetic nephropathy (DN) is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM). Several genome-wide association studies have introduced Engulfment and Cell Motility 1 (ELMO1) as a candidate gene which is associated with DN. This study assessed the association of ELMO1 gene polymorphisms with DN in order to investigate the effects of ELMO1 gene on susceptibility to DN in an Iranian population. Methods In the present study, 100 patients with T2DM, 100 patients with DN and 100 healthy subjects who were matched for sex were selected. Allele and genotype frequencies were determined by Tetra-ARMS PCR technique. In all groups, levels of FBS, creatinine, urea, HbA1C, urine levels of albumin creatinine ratio and glomerular filtration rate were measured. Results A statistically significant association was shown between G allele of rs741301 (odds ratio (OR) = 1.7 [95 % CI 1.17–2.63]; p value = 0.005), and GG genotypes of rs741301 (OR = 2.5 [95 % CI 1.2–5.4]; p value = 0.01) and DN. A significant association was not detected between allelic and genotypic frequencies of rs1345365 and DN. Linkage Disequilibrium (LD) between two variants was weak (D' = 0.11, r2 = 0.008). rs1345365A/rs741301A haplotypes were more frequent in patients with T2DM as compared to DN (OR = 0.5 [95 % CI 0.3–0.7]; p value = 0.0006). Also, genotypes of variant rs741301 in all subjects had significant difference with respect to the mean of ACR (p Value

OBJECTIVE: The aim of this study was to investigate the relationship between the high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and homocysteine (Hcy) levels and cardiometabolic risk factors in subjects with and without metabolic syndrome (MetS) in a sample of the Tehranian population. METHODS: In this cross-sectional study, 365 individuals aged ≥ 19 years were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). The serum levels of IL-6, hsCRP and Hcy were determined using the Enzyme Linked Immunosorbent Assay (ELISA) method. RESULTS: Of the 365 subjects, aged a mean of 46.1 ± 16.1 years, MetS was present in 160 (43.8%) individuals. The levels of hsCRP, Hcy and IL-6 were higher in the subjects with MetS. A gradual and significant increase in the levels of hsCRP was found in association with increasing numbers of MetS components after adjusting for sex and age. A strong linear augmentation in the hsCRP levels was observed as the numbers of MetS components increased. Additionally, an increase of 0.40 was observed in the hsCRP levels in association with increases in each component of MetS adjusted for age and sex. The best predictors for the levels of hsCRP, IL-6 and Hcy in the subjects with MetS were hip, waist to height ratio (WHtR) and height, respectively. CONCLUSION: Hip and WHtR are significant predictors of elevated levels of hsCRP and IL-6 associated with MetS, respectively.