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Background: Tumor necrosis factor-alpha (TNF-α) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometriosis due to the presence of cytokines such as TNF-α. This study aimed to examine the association of four TNF-α polymorphisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population. Materials and Methods: We recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The allele frequency of TNF-α -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjusting for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028). Conclusion: For the first time the association of the four polymorphisms in the promoter region of the TNF-α gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis. [ABSTRACT FROM AUTHOR]

Introduction: Cleft lip/palate is one of the most common congenital defects and is supposed to have multifactorial etiology, including a complex interaction between genetics and environment. Reduced folate carrier 1 (RFC1) gene takes part in folate transportation within the cells. In this study, the association of A80G polymorphism in the RFC1 gene with the nonsyndromic cleft lip/palate (nsCL/P) was investigated in Iranian infants for the first time. Methods: In this case-control survey, 122 Iranian infants with nsCL/P and 164 healthy infants were investigated for RFC1 polymorphism by PCR and RFLP methods. The results were statistically compared with control group, odds ratios with 95% CI were estimated by univariate and multivariate logistic regression model and a P <0.05 was considered statistically significant. Results: The RFC1 G allele was significantly higher (P=0.001; OR=7, 95% CI: 4.7-10.2) in the cases (60.3%) compared with the controls (17.9%). Not only the RFC1 AG genotype was significantly higher (P<0.001; OR=44, 95% CI: 14.6-133) in cases (67.8%) than the controls (27.4%), but also GG genotype (P<0.001; OR=85, 95% CI: 20.5- 352) was much higher in cases (26.4%) than the controls (4.3%). Conclusion: Our study indicated that the RFC1 (A80G) polymorphism was associated with the nsCL/P in Iranian population. Moreover, 80GG homozygosity was significant in the cases. The presence of G allele can be considered as a risk factor for the nsCL/P. Infants with the GG and AG genotypes were more prone to cleft lip/palate as compared to the AA ones. This finding emphasizes the role of RFC1 gene and the intracellular levels of folate. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α ( TNF-α), a multifunctional proinflammatory cytokine, and vascular endothelial growth factor ( VEGF), a major mediator of angiogenesis and vascular permeability, have been investigated in endometriosis patients of different populations. This study was carried out to investigate whether the two polymorphisms, TNF-α −1031T/C and VEGF + 450G/C are associated with susceptibility to endometriosis in an Iranian population. Totally, 135 women with diagnosis of endometriosis and 173 women with no evidence of the disease were included in this study. The −1031T/C and +450G/C polymorphisms were assessed by PCR-RFLP analysis, using the two restriction enzymes BbsI and BsmFI, respectively. The frequencies of the TNF-α −1031TC genotype ( p = 0.038) and the −1031 C allele ( p = 0.048) were significantly lower in patients than control group. In contrast, no significant differences in the genotype and allele frequencies of the VEGF + 450G/C polymorphism were found between the case and control groups. Our results suggest that the TNF-α −1031T/C polymorphism was associated with susceptibility to endometriosis in Iranian population, and the −1301C allele may have a protective role in development of endometriosis; On the contrary, we find no association between the VEGF + 450G/C polymorphism and risk of endometriosis. [ABSTRACT FROM AUTHOR]

Problem Mutations in genes related to thrombophilia and hypofibrinolysis have been associated with recurrent pregnancy loss ( RPL) and polycystic ovary syndrome ( PCOS). Methods Using PCR- RFLP, we investigated the frequencies of MTHFR ( A1298 C and C677 T) as well as PAI-1 (-675 4 G/5 G) gene polymorphisms in 177 RPL and 100 control women. RPL women were stratified into 38 women with PCOS ( RPL- PCOS), 33 with ovarian PCO ( RPL-ovarian PCO), and 106 without PCOS ( RPL). Results RPL, RPL- PCOS, and RPL-ovarian PCO groups showed significantly higher frequencies of MTHFR A1298 C ( P < 0.001) and PAI-1 4 G/5 G ( P < 0.001) mutations than the controls. No significant differences were found between the RPL groups. The respective odds ratios ( OR) for bearing MTHFR ( A1298C, C677 T) and PAI-1 (4G/5G) gene mutations were 33.9-, 2.2-, and 5.2-fold higher in RPL, 66.3-, 6.7-, and 2.8-fold higher in RPL- PCOS, and 27.3-, 1.9-, and 3.9-fold higher in RPL-ovarian PCO women than those in controls. Conclusion Our results showed the significance of MTHFR A1298 C and PAI-1 4 G/5 G mutations in Iranian women suffering from RPL with and without PCOS. [ABSTRACT FROM AUTHOR]

Background: Orofacial cleft is the most common congenital defect of the maxillofacial region. Its non-syndromic type is multi-factorial, and several genes are involved in its occurrence. This study aimed to assess the interaction effect of Rsal and BamHI polymorphisms of Transforming Growth Factor-alpha (TGFα) gene and Bone Morphogenetic Protein-2 (BMP2) and BMP4 variants on the occurrence of Non-Syndromic Cleft Lip and Palate (NSCLP) in the Iranian population. Methods: This case-control study was conducted on 120 children with NSCLP and 215 healthy children. Genotyping of the TGFA/BamHI (rs11466297), TGFA/RsaI (rs3732248), BMP4 (rs17563) and BMP2 (rs235768) was performed by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. Logistic regression was applied to determine the effective factors and the interaction effect of different variants on the occurrence of NSCLP. Results: Gender of patients had no significant association with the occurrence of NSCLP (p=0.335). Multiple logistic regression showed that the interaction effect of the aforementioned polymorphisms on the occurrence of NSCLP was not statistically significant (p=1.000). Conclusion: Although the individual effect of each of the BMP4, BMP2, RsaI and BamHI variants on the occurrence of NSCLP in the Iranian population has been previously confirmed, their interaction does not play a role in this respect. [ABSTRACT FROM AUTHOR]

Background: Nonsyndromic cleft lip and/or palate (NSCL/P) is the most common orofacial birth defect, often attributed to ethnic and environmental differences. Up to now, linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL/P. The WNT genes including WNT3 are strong candidates for NSCL/P, since they are involved in regulating mid-face development and upper lip fusion. This study tested association of the WNT3 polymorphisms, rs- 3809857 G/T and rs9890413 G/A, with the risk of NSCL/P in a population of Iranian in- fants. Methods: The allelic and genotypic frequencies for each participant were determined in 113 unrelated Iranian subjects with NSCL/P and 220 control subjects using PCR and restriction fragment length polymorphism (RFLP) methods. A p-value of ≤0.05 was considered statistically significant. Results: The WNT3 rs3809857 GT genotype was significantly lower (p=0.039, OR=0.55, 95% CI=0.30-0.97) in the NSCL/P (21.2%) than the control group (30.42%). For the WNT3 rs9890413 G/A polymorphism, neither genotype nor allele frequencies were sig- nificantly different between the case and control groups. Conclusion: Our results indicated that the WNT3 rs3809857 GT genotype may have a protective effect against NSCL/P in Iranian population. [ABSTRACT FROM AUTHOR]

Background: Endometriosis influenced by both genetic and environmental factors. Associations of glutathione S-transferases (GSTs) genes polymorphisms in endometriosis have been investigated by various researchers; however, the results are not consistent. Objective: We examined the associations of GSTM1 and GSTT1 null genotypes and GSTP1 313 A/G polymorphisms with endometriosis in an Iranian population. Materials and Methods: In this case-control study, 151 women with diagnosis of endometriosis and 156 normal healthy women as control group were included. The genotyping was determined using multiplex PCR and PCR- RFLP methods. Results: The GSTM1 null genotype was significantly higher (p=0.027) in the cases (7.3%) than the control group (1.3%). There was no significant difference between the frequency of GSTT1 genotypes between the cases and controls. The GSTP1 313 AG genotype was significantly lower (p=0.048) in the case (33.1%) than the control group (44.4%). Conclusion: Our results showed that GSTM1 and GSTP1 polymorphisms may be associated with susceptibility of endometriosis in Iranian women. [ABSTRACT FROM AUTHOR]

Introduction: Late-onset Alzheimer's Disease (LOAD) is a neurodegenerative disorder and the most common form of dementia affecting people over 65 years old. Alzheimer's disease is a complex disease with multi-factorial etiology. Inflammation has been approved to have an important role in the pathogenesis of Alzheimer's disease (AD). TNF-α is a main pro-inflammatory cytokine that plays an essential role in initiation and regulation of inflammatory responses. Several studies have shown the probable association of polymorphism at TNF-α gene's promoter with AD pathogenesis. This study was performed to determine whether this polymorphism contributes to the risk for late-onset Alzheimer's disease (LOAD) in Iranian population. One hundred and forty AD patients and 158 healthy controls were recruited in the study. Following extraction of genomic DNA, using PCR/RFLP methods the genotype and allele frequencies were determined in case and control subjects. The statistical analysis showed no significant difference in the allele and genotype frequencies due to this polymorphism between the two groups. Also after stratifying the subjects by their APOE-ϵ4 status, no significant association was observed. Our results suggest that Tumor necrosis factor-alpha (TNF-α) -308 G/A is not a risk or protective factor for late-onset Alzheimer's disease in Iranian population. However, to confirm these results further study with a bigger sample size may be required. [ABSTRACT FROM AUTHOR]