Effects of HRG and TP73 gene variations on ovarian response.

AIMS: This study aims to investigate whether HRG gene C633T rs9898 and TP73 gene rs4648551 A > G polymorphisms have an effect on ovulation and response to the gonadotropin treatments. MATERIALS AND METHODS: Blood samples were received from a total of 206 individuals (116 patients from whom good quality and optimal of numbers oocytes have not been able to be obtained at the IVF Center of Ondokuz Mayis University, Faculty of Medicine and 90 controls). Genomic DNA was extracted by DNA isolation and SNP genotyping was performed by real-time qPCR method. RESULTS: According to the results, a significant difference was observed between the patient and control groups in terms of the TP73 gene variant, however there was no significant difference regarding HRG gene polymorphism. CONCLUSIONS: Our findings suggest that while AG genotype for TP73 could be a genetic marker for ovarian response, HRG gene C633T variation is not associated with ovarian response in our cohort. Further studies with larger study groups are required to investigate possible associations of these gene variants with ovarian response.

Chromosomal microarray analysis of patients with Duane retraction syndrome.

PURPOSE: Duane retraction syndrome (DS) is a rare congenital strabismus with genetic heterogeneity. The genetic causes of DS are not always of monogenic origin; various chromosomal copy number variations (CNVs) have also been reported. The objective of our study was to characterize the CNVs, including gains and losses detected by high-resolution chromosomal microarray in patients with DS. METHODS: Twenty patients with DS were investigated using high-resolution chromosomal microarray analysis (CMA) (Affymetrix CytoScan Array 750 K). Conventional cytogenetic analysis was also performed. RESULTS: All samples revealed normal karyotype by cytogenetic analysis. However, in all our patients, multiple CNVs, including gains and losses, were detected using the high-resolution CMA method. Chromosomal loci 1q21.2, 2p11.2-q11.1, 2q21.1-q21.2, 4p16.1, 7p11.2-q11.21, 14q32.33, 17p11.2-q11.1 and 20p11.1-q11.21 were the most frequently affected regions. CONCLUSIONS: This study emphasized that CNVs in several chromosomal regions are known to be involved in DS. We also underscore the genetic heterogeneity of DS. Our suggestion is that genes located in the most frequently affected regions should be focused on in the following candidate gene studies.

Effects of subtelomeric copy number variations in miscarriages.

PURPOSE: This study was performed on miscarriage samples for chromosome analysis to detect copy number variations (CNVs) related to subtelomeric regions, and with these results we aimed to adapt multiplex ligation-dependent probe amplification (MLPA) method for prenatal diagnosis. MATERIALS AND METHODS: The cell cultures and DNA isolations were performed on 60 miscarriage samples. For maternal contamination analysis, DNA isolations and quantitative fluorescent polymerase chain reactions were done using peripheric blood of mothers who had miscarriages. We compared short tandem repeat peak profiles of miscarriage samples and mothers. The subtelomeric regions of the chromosomes were assessed using the MLPA method. RESULTS: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%). Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples investigated with MLPA method (6.6%). CONCLUSION: There is no statistically significant difference between two groups (p > 0.05). However, the fact that the 6.6% subtelomeric CNV found in miscarriage samples was not found in controls, showed that further studies are required. We recommend that the miscarriage samples of the couples with recurrent miscarriage should be analyzed in terms of subtelomeric CNV after the exclusion of other clinical reasons.

FMR1 gene mutation screening by TP-PCR in patients with premature ovarian failure and fragile-X.

CGG repeat expansion in the FMR1 gene is associated with fragile X syndrome, fragile X-associated tremor/ ataxia syndrome and fragile X-associated primary ovarian insufficiency. In this study, FMR1 gene mutation screening was carried out in 50 patients. Among them, 12 (%24) were POF and 19 (%38) were Fragile-X. We also examined the parents of the Fragile-X patients. DNA was extracted from blood with kit procedure. To examine expansion of the fragile-X CGG repeat, TP-PCR assay was performed and all amplicons were evaluated on an ABI3130XL Genetic Analyzer System by Fragman analysis. The data were analyzed by Gene Mapper Program. As a result of this study, the patients were identified with the fragile-X whose FMR1 gene CGG alleles have been observed in normal range. However, in patients who were referred with premature ovarian failure, pre-mutation frequency was observed as 6.6%. Only limited study in Turkish population reported frequency of pre-mutation carrier in POF and Fragile-X. Detection of pre-mutation carrier is important for next generation to have healthy siblings. We emphasize that TP-PCR technique is clear, reliable, sensitive, easy and fast method to detect pre-mutation. However, full mutations have to be examined by the technique of Southern blot in the diagnosis of fragile-X.

The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever.

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.

Effects of leptin and leptin receptor gene polymorphisms on lung cancer.

Leptin (LEP), an adipocyte-derived cytokine, has been reported to participate in carcinogenesis. Elevated levels of systemic and pulmonary LEP are associated with diseases related to lung injury and lung cancer. The purpose of the present study was to investigate if the LEP and leptin receptor (LEPR) gene polymorphisms are associated with lung cancer in a cohort of Turkish population. One hundred and sixty-two lung cancer patients and 130 healthy controls were included in the study. The genotypes of LEP gene -2548G > A and LEPR gene Q223R polymorphisms were determined using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. The genotype frequencies of LEP -2548G > A polymorphism showed statistically significant differences between lung cancer patients and controls (p = 0.007). GA + AA genotypes and A allele of LEP -2548G > A polymorphism was found to be susceptibility factors for lung cancer (p = 0.003, odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.32-4.10; p = 0.003, OR 1.65, 95 % CI 1.18-2.29, respectively). The genotype and allele frequencies of LEPR Q223R polymorphism did not show any statistically significant differences between lung cancer patients and controls (p = 0.782 and p = 0.762, respectively). Although AA-QQ and AA-QR combined genotypes of LEP -2548G > A-LEPR Q223R loci were significantly higher in lung cancer patients (p = 0.020 and p = 0.047, respectively), GG-QQ, GG-QR, and AA-RR combined genotypes were significantly higher in control group. As a result, susceptibility effects of LEP -2548G > A polymorphism alone or in combination with LEPR Q223R polymorphism on lung cancer were observed. Further studies are necessary to prove the association of LEP and LEPR gene polymorphisms with lung cancer.

The combined QF-PCR and cytogenetic approach in prenatal diagnosis.

In this study, the importance of quantitative fluorescence polymerase chain reaction (QF-PCR) aneuploidy diagnosis test which provides earlier and easier results were discussed. The cell cultures and DNA isolations were performed on 100 amniotic fluids. DNA isolations were made from peripheral blood samples of mothers who had blood-stained amniotic fluid samples. The reasons of references of these pregnant women to our division were increased maternal age, positive double/triple screening test and fetal anomaly history. QF-PCR applied to 19 short tandem repeat markers in the chromosomes 13, 18, 21 and genes X and Y chromosomes. All electropherogram peaks were evaluated on ABI3130. Thirty two (32%) samples have high maternal age, seven (7%) have fetal anomaly and the others have double/triple screening test positivity. Ninety-nine (99%) of the 100 amniotic fluid samples were resulted, but one (1%) of them could not examined because of the culture failure. The maternal contamination rates were determined as 3%. Of 100 samples, 2 had trisomy 21 (2%), 1 had trisomy 13 (1%), 1 had structural abnormalities (1%) and the others (97%) have not any aneuploidy. The results of QF-PCR were in compatible with the results of cell culture and chromosome analysis. Although QF-PCR is an easier and an earlier test, it has a limitation of not to able to scan full genome. It is also sensitive for maternal contamination, so it should be tested together with maternal blood samples. QF-PCR aneuploidy test is the fastest diagnostic test for prenatal diagnosis and so it provides less stressful period for pregnant women.

Promoter methylation status of RASSF1A and RASSF2A tumor suppressor genes in endometrial endometrioid carcinomas.

We aimed to investigate the promoter methylation status of RASSF1A and RASSF2A tumor suppressor genes in endometrial endometrioid carcinomas with p53 wild type and mismatch repair proficient. Genomic DNAs were isolated from 50 specimens (15 formalin-fixed paraffin embedded tumor tissues, 15 paired blood samples and 20 normal endometrial tissues). Bisulfide modification and methylation-specific polymerase chain reaction were performed. As a result of the study, while no significance was found for RASSF1A gene (p = 0.08), a statistically significance was found for RASSF2A gene (p < 0.001), RASSF2A gene methylation status was also found higher in high grade tumors, advanced age (≥50) and nonsmokers groups. Our results indicate that RASSF2A gene may play a role in the carcinogenesis of endometrioid and it could be potential biomarker for early detection for endometrioid carcinoma. Further and larger investigations are needed to confirm our results.

Association of IL-4 gene VNTR variant with deep venous thrombosis in Behçet's disease and its effect on ocular involvement.

PURPOSE: Behçet's disease (BD) is a systemic vasculitis characterized by inflammatory lesions of the urogenital mucosa, eyes, skin, central nervous system, and joints. Vein thrombosis constitutes the most frequent vascular manifestation of the disease, and may cause such ocular vascular thrombotic events as central retinal vein and central retinal artery thrombosis. Thrombosis is a serious problem, and often leads to irreversible vision loss. Previous studies have shown that genetic factors predispose individuals to BD. Several cytokine genes might play crucial roles in host susceptibility to BD and to thrombophilia. Various polymorphic regions of the interleukin-4 (IL-4) gene (-1098G and 590T) are associated with BD in the Turkish population. This study was conducted in Turkish patients with BD to determine the frequency of the IL-4 gene 70 bp variable number of tandem repeats (VNTR) variant, and its association with clinical findings. METHODS: Genomic DNA obtained from 488 individuals (238 patients with Behçet's disease and 250 healthy controls) was used in the study. Genomic DNA was isolated and genotyped using PCR assay for the IL-4 gene 70 bp VNTR polymorphism determined by using PCR with the specific primers. RESULTS: There was statistical significance between the groups regarding IL-4 genotype distribution (p<0.001, odds ratio: 2.55 [1.629-4.052], 95% confidence interval) and allele frequencies (p<0.0012.381[1.586-3.617], 95% confidence interval). When we examined IL-4 genotype frequencies according to the clinical characteristics, we observed a statistically significant association between the P2P2 genotype and deep venous thrombosis (p=0.01). Deep venous thrombosis was also associated with ocular involvement in our study group (p=0.014). CONCLUSIONS: Our findings suggest that the IL-4 gene 70 bp VNTR polymorphism is associated with susceptibility to development of BD. Deep venous thrombosis is also associated with ocular involvement in BD. The IL-4 gene could be a genetic biomarker in Behçet's disease in a Turkish study population.

DD genotype of ACE gene I/D polymorphism is associated with Behcet disease in a Turkish population.

Behcet's disease (BD) is a chronic, multi-systemic and inflammatory disorder. The local renin-angiotensin system (RAS) in the vessel wall plays a role in the endothelial control and contributes to inflammatory processes. Angiotensin-converting enzyme (ACE) is the regulatory component of the RAS. This study was conducted in Turkish patients with BD to determine the frequency of I/D polymorphism genotypes of ACE gene. Genomic DNA obtained from 566 persons (266 patients with BD and 300 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. There was statistically significant difference between the groups with respect to genotype distribution (p < 0.001). This study is the largest study in Turkish population that ACE gene I/D polymorphism investigated in BD. As a result of this study, ACE gene I/D polymorphism DD genotype could be a genetic marker in BD in Turkish study population.

Vascular endothelial growth factor gene insertion/deletion polymorphism is associated with Vitamin D level in Turkish patients with coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 emerges as a disease caused by severe acute respiratory syndrome coronavirus 2. It is a systemic disease associated with vascular inflammation and endothelial damage. In this study, we aimed to investigate whether vascular endothelial growth factor gene insertion/deletion polymorphism is associated with coronavirus disease 2019 in the Turkish population. METHODS: The study included 179 participants (79 patients with coronavirus disease 2019 and 100 controls). DNA isolation was made from peripheral blood, and then the polymerase chain reaction analysis was performed. RESULTS: When we analyze vascular endothelial growth factor gene insertion/deletion polymorphism in the study group, we found that the DD genotype and D allele were found to be statistically significantly different when compared to coronavirus disease 2019 patients with high vitamin D value (p=0.005 for DD genotype and p=0.006 for D allele) in the control group. In this high-level control group, when we analyze II+ID genotype versus DD, a statistically significant difference was also detected (p=0.007). CONCLUSION: As a result of the study, we found that DD genotype and D allele were associated with vitamin D level in Turkish patients with coronavirus disease 2019.

miR604A>G gene polymorphism is associated with recurrent pregnancy loss in Turkish women.

OBJECTIVE: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population. METHODS: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied. RESULTS: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively). CONCLUSION: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis.

PURPOSE: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that characteristically affects the sacroiliac joints and the spine. Also iritis and uveitis can be serious complications of AS that can damage the eye and impair vision. The exact pathogenesis of AS remains poorly understood but genetic factors play a key role in its development. Human leukocyte antigen B27 (HLA-B27) is the major genetic susceptibility marker in AS. To our knowledge, angiotensin converting enzyme (ACE) gene I/D polymorphisms have not yet been investigated in AS patients in Turkish population.This study was conducted in Turkish patients with AS to determine the frequency of I/D polymorphism genotypes of angiotensin converting enzyme gene. METHODS: Genomic DNA obtained from 262 persons (122 patients with ankylosing spondylitis and 140 healthy controls) was used in the study. ACE I/D polymorphism genotypes were determined by using polymerase chain reaction with specific primers. RESULTS: There was statistically significant difference between the groups with respect to genotype distribution (p<0.001). When we examine ACE genotype frequencies according to the clinical characteristics there was a statistically significant association between DD genotype and ocular involvement (p=0.04) also sacroiliac joint involvement (p=0.03). CONCLUSIONS: As a result of our study, angiotensin converting enzyme gene I/D polymorphism DD genotype could be a genetic marker in ankylosing spondylitis in a Turkish study population.

Novel RET Proto-oncogene variants identified in Turkish patients with thyroid carcinoma.

Thyroid cancer is one of the few malignancies whose incidence is increasing in the last decades. Advances in understanding the molecular mechanisms lead to provide opportunity for prevention, effective early identification and targeted therapies for management. A total of 63 patients with participated in this study Genomic DNA samples were obtained from the samples formalin- embedded tissue and peripheral blood. Following polymerase chain reaction amplification of the 6 RET key exons (10, 11, 13, 14, 15, and 16) were applied and PCR products were subjected to next generation DNA sequencing (ABI 3730). Results revealed that; genotype frequencies were for rs1800961 (G > T) , GG 6 (%9.5), GT 17 (%27) TT40 (%63.5) for rs2472732 (G > A), GG31 (%49.2) GA29 (%46) AA3 (%4.8,) for rs1799939, (G > A) GG42 (%66.7) GA19 (%30.2) AA2 (%3.2), for rs1800962, (C > T) CC54 (%85.7) CT9 (%14.3), for rs1800863 (C > G), CC39 (%61.9) CG22 (%34.9) GG2 (%3.2), for rs3026272 (C > G) CC 13 (%20.6) CG 50 (%79.4). Additionally 15 potential novel genetic variants were identified in these key exons. Detailed information was given both known and new detected variants in supplementary table. Genetic variants distribution frequencies and new variants represented in Turkish thyroid cancer patients for RET proto-oncogene and that results would provide contribution to the literature.

Vascular endothelial growth factor gene insertion/deletion polymorphism is associated with Vitamin D level in Turkish patients with coronavirus disease 2019

SUMMARY OBJECTIVE: Coronavirus disease 2019 emerges as a disease caused by severe acute respiratory syndrome coronavirus 2. It is a systemic disease associated with vascular inflammation and endothelial damage. In this study, we aimed to investigate whether vascular endothelial growth factor gene insertion/deletion polymorphism is associated with coronavirus disease 2019 in the Turkish population. METHODS: The study included 179 participants (79 patients with coronavirus disease 2019 and 100 controls). DNA isolation was made from peripheral blood, and then the polymerase chain reaction analysis was performed. RESULTS: When we analyze vascular endothelial growth factor gene insertion/deletion polymorphism in the study group, we found that the DD genotype and D allele were found to be statistically significantly different when compared to coronavirus disease 2019 patients with high vitamin D value (p=0.005 for DD genotype and p=0.006 for D allele) in the control group. In this high-level control group, when we analyze II+ID genotype versus DD, a statistically significant difference was also detected (p=0.007). CONCLUSION: As a result of the study, we found that DD genotype and D allele were associated with vitamin D level in Turkish patients with coronavirus disease 2019.

miR604A>G gene polymorphism is associated with recurrent pregnancy loss in Turkish women

SUMMARY OBJECTIVE: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population. METHODS: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied. RESULTS: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively). CONCLUSION: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

Evaluation of apoptotic cell death on liver and kidney tissues following administration of levetiracetam during prenatal period.

OBJECTIVE: Levetiracetam is a new generation antiepileptic drug used in treatment of patients with epilepsy and has adverse effects on different tissues. We aimed to evaluate the apoptotic effects of levetiracetam exposure during pregnancy on liver and kidney tissues of rat pups. METHODS: We analyzed the newborn rat pups exposed to levetiracetam during prenatal period. Fifteen pregnant female rats were divided into three groups. The group 1 and 2 rats were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d, respectively) from gestational days 1-22 during pregnancy. Group 3 (control group) was treated with the same volume of saline. Apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) method. Liver and kidney tissues from rat pups were used for investigation. RESULTS: The percent of TUNEL positive apoptotic cells in group 1 were 22 and 17.5 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 2 were 20.9 and 20.9 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 3 were 18.4 and 17.1, respectively, for kidney and liver. The apoptotic index was the same in kidney and liver tissues of all groups. CONCLUSION: Our results demonstrate that the prenatal exposure of levetiracetam has no apoptotic effects on liver and kidney of rat pups and, it has biosafety in pregnancy in terms of apoptosis. The first study evaluating the apoptotic effects on liver and kidney tissues following administration of levetiracetam during prenatal period.

Evaluation of CYP17A1 and LEP Gene Polymorphisms in Breast Cancer.

BACKGROUND: Polymorphisms of estrogen synthesis- and adiposity-related genes can contribute to the development of breast cancer. The purpose of the current study was to analyze the association between CYP17A1 T27C (rs743572) and LEP -2548G>A (rs7799039) gene polymorphisms and breast cancer. MATERIAL AND METHODS: 199 breast cancer patients and 197 healthy controls were included in the study. The CYP17A1 and LEP gene polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism analysis. RESULTS: No statistically significant association was found between these polymorphisms and breast cancer risk among a Turkish population. However, stratified analysis of these polymorphisms in relation to different clinicopathological characteristics of breast cancer revealed an association between breast cancer diagnosis and the CYP17A1 T27C polymorphism (p = 0.024). CONCLUSION: Our study suggests no strong association between the CYP17A1 T27C and LEP -2548G>A polymorphisms and the incidence of breast cancer in Turkish women. The potential association between CYP17A1 T27C and the type of breast cancer deserves further consideration.

Genotoxic effects of prenatal exposure to levetiracetam during pregnancy on rat offsprings.

Levetiracetam is a new-generation antiepileptic drug initially approved as an adjunctive treatment for patients with refractory partial seizures and is now also used as a monotherapy. The aim of this study was to evaluate the genotoxic effects of levetiracetam exposure during pregnancy on rat offsprings. In this study, we used the newborn pups of rats exposed to levetiracetam during pregnancy. Thirty Sprague-Dawley rats were divided into three groups. The mother rats of groups 1 and 2 were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d) from gestational days 1 to 18 during pregnancy. Group 3 (control group) was not treated with any drug. In vivo sister chromatid exchange (SCE) induction and in vivo micronucleus formation were assessed. Bone marrow from rat pups were used for investigation. As a result of this study, levetiracetam exposure did not alter SCE frequencies or the mean of number of micronuclei in the prenatal period (p>0.05). Levetiracetam did not cause miscarriage during pregnancy in mother rats. The present study highlighted fetal safety after prenatal exposure to levetiracetam.

IL-4 and MTHFR gene polymorphism in rheumatoid arthritis and their effects.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that mainly affects the joints. Polymorphic variations of the cytokine genes and MTHFR gene have received attention as potential markers of susceptibility, severity, and/or protection in RA. The aim of this study was to investigate the MTHFR C677T and IL-4 70bp VNTR variation in Turkish patients with RA and evaluate if there was an association with clinical features, especially ocular involvement, in RA patients. The study included 297 persons (147 patients with RA and 150 healthy controls). Genomic DNA was isolated and genotyped using PCR assay for the MTHFR gene C677T and IL-4 gene 70bp VNTR polymorphisms. Our results show that there was statistically significant difference between the groups with respect to IL-4 genotype (p=0.01) and allele frequencies (p<0.002). There was no statistical significant difference in the genotype frequencies MTHFR gene, but allele frequencies showed statistically significant association (p=0.01). When we examined MTHFR and IL-4 genotype frequencies according to the clinical characteristics, we found that there was a difference between MTHFR genotypes and ocular involvement but it is not to a statistical significant degree (p=0.09). In the combined genotype analysis, MTHFR/IL-4 CCP2P2 combine genotype was estimated to have protective effect against RA, CTP1P2 combine genotype was found to be risk for RA. Our findings suggest that there is an association of IL-4 gene 70bp VNTR polymorphism and MTHFR C677T polymorphism with susceptibility of a person for development of RA.