Serbulent Yigit

Significance of MEFV gene R202Q polymorphism in Turkish familial Mediterranean fever patients

OBJECTIVE Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. The disease is associated with mutations in the Mediterranean fever (MEFV) gene, which encodes for the pyrin protein. The aim of this study was to explore the frequency and clinical significance of the R202Q (c.605G>A) polymorphism in exon 2 of the MEFV gene in a cohort of Turkish patients with FMF. METHODS The study included 191 patients with FMF and 150 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MEFV gene R202Q polymorphism. RESULTS The genotype and allele frequencies of R202Q polymorphism showed a statistically significant difference between FMF patients and controls (p<0.0001 and p=0.0004, respectively) and especially the homozygous AA genotype was significantly higher in FMF patients than healthy controls (p=0.0002; odds ratio=6.27; 95% CI=2.1-18.3). However no significant association was observed between clinical and demographic features of FMF patients and R202Qpolymorphism. CONCLUSION The results of this study showed that there was a high association between MEFV gene R202Q polymorphism and FMF. R202Q polymorphism should be included in routine molecular diagnosis of FMF patients.

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.

The association between Interleukin (IL)-4 gene intron 3 VNTR polymorphism and alopecia areata (AA) in Turkish population.

OBJECTIVE Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease of hair follicles mediated by T cells. As immunological and genetic factors have been implicated in the pathogenesis of AA, the purpose of the present study was to investigate possible associations between the functional Interleukin (IL)-4 gene intron 3 VNTR polymorphism and AA susceptibility and disease progression in Turkish population. METHODS The study group consisted of 116 unrelated patients with AA and 125 unrelated healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers. RESULTS No association was observed between AA patients and controls according to genotype distribution (p=0.051). The allele distribution of IL-4 gene intron 3 VNTR polymorphism was statistically different between AA patients and control group (p=0.026). The frequency of P1 allele in patients was significantly higher than that in the control group. When the P2P2 genotype was compared with P1P2+P1P1 genotypes, a statistically significant difference was observed between patients and controls (p=0.036). Intron 3 VNTR polymorphism in the IL-4 gene was found to be associated with AA susceptibility in Turkish population. CONCLUSION The results suggest that IL-4 VNTR polymorphism in the intron 3 region may be a risk factor for the development of AA among Turkish population. This is the first to report that intron 3 VNTR polymorphism in the IL-4 gene is associated with AA susceptibility.

The importance of association between angiotensin-converting enzyme (ACE) Gene I/D polymorphism and diabetic peripheral neuropathy.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus (DM) due to decreasing quality of life. In the present study, it is aimed to evaluate angiotensin-converting enzyme (ACE) Gene I/D polymorphism in Turkish population. MATERIALS AND METHODS Two hundred and thirty-five DPN patients and two hundred and eighty-one controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the ACE gene I/D polymorphism. RESULTS Baseline characteristics of the DPN patients according to ACE genotypes were similar, except for history of hypertension. The frequency of II genotype was significantly higher in patients with positive history of hypertension than the patients with negative history of hypertension (p=0.013). DD genotype of I/D polymorphism was found to be a susceptibility factor for DPN in homozygous form (p=0.032). According to allele frequencies, D allele of I/D polymorphism was found to be a susceptibility factor for DPN (p=0.031). CONCLUSION ACE gene I/D polymorphism may research in DM patients to determine genetic predisposition for DPN. It can be useful for taking early measures and avoiding DPN in a Turkish population.

Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenesis is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5-flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay; supernatant levels of LDH and glucose were detected as biochemical markers of cell viability; cytochrome c and AIF were evaluated with western blot; and additionally, wound-healing assays were employed. Results suggested that capsaicin had significant anticancer abilities; such capsaicin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used for treating gastric carcinoma with 5-FU in vitro.

Common MEFV gene mutations in Turkish patients with Behcet's disease

Behcets disease (BD) is a chronic systemic inflammatory disorder whose etiology has not been fully established yet. The MEditerranean FeVer (MEFV) gene has been identified as the cause of Familial Mediterranean Fever (FMF). BD shows similarities with FMF, in terms of clinical findings and treatments, as well as their geographical and ethnic co-occurrence. In this study we investigated common MEFV gene mutation frequencies in Turkish patients with BD in an area of Turkey where both diseases are frequently encountered. We screened 207 BD patients who had no symptoms and family history for FMF and 200 healthy subjects for five common MEFV gene mutations (E148Q, M680I, M694V, V726A, P369S) and clinical features. Seventy-five patients were found to carry a single MEFV mutation, and six patients were compound heterozygous. The difference in the frequency of the MEFV mutation between the BD and control groups was statistically significant (p<0.001, odds ratio [OR] 2.74, 95% confidence interval [CI] 1.75-4.29). The frequencies of E148Q and M680I mutations were significantly higher in the BD group (p=0.001, p=0.046, respectively). The frequency of uveitis was significantly lower in patients with the mutation than in patients without the mutation (p=0.029, OR 0.54, 95% CI 0.30-0.98). There was no statistical significance between carriers and non-carriers with respect to gender and other manifestations of BD. The frequency of the MEFV mutation was significantly higher in patients with BD compared to the healthy control group. Based on our results, MEFV mutations appear to have a role in the pathogenesis of BD.

Investigation of associations between obesity and LEP G2548A and LEPR 668A/G polymorphisms in a Turkish population.

Objective. Obesity is a complex heterogeneous disease that is caused by genes, environmental factors, and the interaction between the two. The leptin (LEP) and leptin receptor (LEPR) genes have been evaluated for polymorphisms that could potentially be related to the pathophysiology of obesity and its complications. The aim of this study was to investigate the role of LEP G2548A and LEPR 668A/G polymorphisms in the pathogenesis of obesity. Subjects. The study included 127 patients with obesity and 105 healthy controls. Polymerase chain reaction and restriction fragment length analysis for LEP G2548A and LEPR 668A/G polymorphisms were applied. Results. There was no statistically significant difference in the genotype frequencies of the LEP gene polymorphism between patients and control groups (P > 0.05). We found a difference in the LEPR genotypes between patients and controls, but this was not statistically significant (P = 0.05). Additionally, we found an increased risk of obesity in the LEP/LEPR GG/GG combined genotype (P < 0.05). Conclusion. Our findings indicate that the LEP G2548A polymorphism is not a relevant obesity marker and that the LEPR 668A/G polymorphism may be related to obesity in a Turkish population. Further researches with larger patient population are necessary to ascertain the implications of LEP and LEPR polymorphisms in obesity.

High Association of IL-4 Gene Intron 3 VNTR Polymorphism with Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common disease. It is one of the late complications of diabetes mellitus. DPN can lower the quality of life by causing severe painful clinic symptoms. The aim of this study is to evaluate interleukin (IL)-4 gene variable number of tandem repeat (VNTR) polymorphism on DPN in Turkish population. Two hundred and twenty-seven DPN patients and 241 controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction analyses for the IL-4 gene intron 3 VNTR polymorphism. The distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between DPN patients and control group (p = 0.001). The frequency of P1 and P2 alleles was statistically different between DPN patients and control group (p = 0.00009). The results of this study suggested that intron 3 VNTR polymorphism of the IL-4 gene plays an important role in the occurrence of DPN in the Turkish population.

Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients.

OBJECTIVE Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases, with a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. The purpose of the present study was to investigate a possible association between the functional interleukin 4 (IL4) VNTR genetic polymorphism and RAS in a sample of Turkish patients. METHODS The study included 145 unrelated patients with a clinical diagnosis of RAS and 150 unrelated healthy controls. Genomic DNA was isolated and IL4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers. RESULTS The distribution of genotype and allele frequencies of IL4 gene intron 3 VNTR polymorphism was statistically different between RAS patients and control group (p<0.0001 and p<0.0001, respectively) P2P2 genotype and P2 allele were also found to be protective with a lower risk for susceptibility to RAS (p<0.0001). CONCLUSION The results of this study suggest that intron 3 VNTR polymorphism in the IL4 gene is associated with RAS susceptibility in Turkish population.

Analysis of common MDR1 (ABCB1) gene C1236T and C3435T polymorphisms in Turkish patients with familial Mediterranean fever

The multidrug resistance (MDR1) gene encodes a P-glycoprotein that plays a key role in drug bioavailability and response to drugs in different human populations. More than 50 SNPs have been described for the MDR1 gene. Familial Mediterranean fever (FMF) is considered an autosomal recessive hereditary disease, associated with a single gene named the Mediterranean fever gene (MEFV). However, about one-third of FMF patients have only one mutated allele, suggesting that this disease is expressed as an autosomal dominant trait with partial penetration or an additional gene might be responsible for the disease. We made genotype and haplotype analyses of the MDR1 gene in 142 FMF patients and 130 unrelated Turkish subjects; two MDR-1 genetic markers (C1236T and C3435T) were analyzed by PCR-RFLP analysis. FMF patients had a significantly higher frequency of the 3435 CT genotype compared with the control group (59.9% in FMF patients versus 44.6% in controls; odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.14-3.00). Based on haplotype analysis, the T-C shift was significantly more frequent in controls (14.4% versus 7.1% in FMF patients). This haplotype could be protective for FMF disease (OR = 0.45; 95%CI = 0.25-0.84). The frequency of CC-CT (1236-3435) binary genotype was significantly higher in FMF patients (14.79% versus 4.61% in controls; OR = 3.59; 95%CI = 1.40-9.20).