The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians

Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.     

2型糖尿病家系患者LEPR基因Gln223Arg多态性的研究

目的：研究黑龙江地区汉族人2型糖尿病家系的LEPR基因Gln223Arg多态性,探讨其与2型糖尿病发病的关系。方法：应用聚合酶链式反应-限制性内切酶长度多态性（PCR-RFLP）技术,对来自于黑龙江地区120个2型糖尿病家系中的210例2型糖尿病患者及319例正常对照的LEPR基因Gln223Arg（668 A→G）位点进行基因分型。结果：LEPR基因Gln223Arg三种基因型在病例组和对照组间整体分布有统计学意义（P=0.034,df=2）;除AG基因型（x2=4.550,P〈0.01）外,其余各基因型及等位基因在病例组和对照组间分布未见显著性差异（P〉0.05）。结论：LEPR基因Gln223Arg多态性与黑龙江地区汉族人2型糖尿病有关,LEPR基因可能为中国人2型糖尿病发病的相关易感基因。     

XRCC1 Arg399Gln gene polymorphism and the risk of systemic lupus erythematosus in the Polish population

It has been shown that DNA repair is reduced in patients with systemic lupus erythematosus (SLE) and that the X-ray repair cross-complementing (XRCC1) Arg399Gln (rs25487) polymorphism may contribute to DNA repair. We evaluated the frequency of the XRCC1 Arg399Gln substitution in patients with SLE (n=265) and controls (n=360) in a sample of the Polish population. The odds ratio (OR) for SLE patients with the Gln/Gln versus Gln/Arg or Arg/Arg genotypes was 1.553 (95% confidence interval [CI]=0.9573-2.520; p=0.0729). OR for the Gln/Gln or Gln/Arg versus Arg/Arg genotype was 1.551 (95% CI=1.122-2.144, p=0.0077). The OR for the 399 Gln allele in patients with SLE was 1.406 (95% CI=1.111-1.779, p=0.0045). There was also a statistically significant p-value of the χ(2) test for the trend observed in the XRCC1 Arg399Gln polymorphism (ptrend=0.0048). We also found a significant contribution of the Gln/Gln or Arg/Gln versus Arg/Arg genotype to the presence of either the malar rash or photosensitivity manifestations of SLE OR=2.241 (1.328-3.781, p=0.0023, pcorr=0.0414). Moreover, the meta-analysis of Taiwanese Han Chinese, Brazilian, and Polish populations showed that the Gln/Gln or Gln/Arg genotype and Gln allele were associated with SLE incidence. OR for the Gln/Gln or Gln/Arg versus Arg/Arg genotype was 1.440 (95% CI=1.15-1.80, p=0.0019) and OR for the Gln allele was 1.27 (95% CI=1.08-1.51, p=0.0051). Our studies may confirm that the XRCC1 Arg399Gln polymorphism may increase the risk of incidence of SLE and the occurrence of some SLE manifestations.     

Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians

The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene.     

Joint effect of G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism on the risk of premature coronary artery disease

The study sought an association between the G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism and premature coronary artery disease (CAD), and the interactive effect on CAD risk between the G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism as well as between tested polymorphisms and traditional risk factors. 167 patients with CAD younger than 55 years were compared with 132 healthy subjects. The frequency of factor V point mutation was 7.8 % among Slovene patients with premature CAD, and 4.5 % among controls. No association was found between either the factor V point mutation (AG genotype) or M1M1 genotype of factor VII Arg/Gln(353) gene polymorphism and the risk of CAD in Slovenia using univariate analysis (factor V point mutation: OR = 1.8, 95% CI = 0.7-4.9; p = 0.25; factor VII Arg/Gln(353) gene polymorphism: OR = 1, 95 % CI = 0.6-1.7; p = 0.9). However, a joint effect on the risk of CAD was found between factor V point mutation (AG genotype) and M1M1 genotype (OR = 3.6, 95 % CI = 1-12.9; p = 0.03). Additionally, an interactive effect on CAD risk was found between AG genotype and metabolic risk factors (OR = 3.8, 95% CI = 1.1-13.6; p = 0.03). In conclusion, we provide evidence for a joint effect on CAD risk between G1691A factor V point mutation and factor VII Arg/Gln(353) gene polymorphism as well as between factor V point mutation and metabolic risk factors.     

The C-174G promoter polymorphism of the interleukin-6 (IL-6) gene that affects insulin sensitivity in Caucasians is not involved in the pathogenesis of Taiwanese type 2 diabetes mellitus

Interleukin-6 (IL-6) is a pleiotropic cytokine which regulates the immune response, the acute-phase response, hematopoiesis and body energy balance. Genetic polymorphism at -174 position of IL-6 promoter has been recently reported to be linked with insulin resistance, however, with conflicting results. The C allele at IL-6 -174 position is associated with increased insulin sensitivity, and has a protective role for the development of type 2 diabetes, in a Spanish study. Whereas, according to a Finnish study, it is correlated with lower insulin sensitivity and may encourage the development of type 2 diabetes. Ethnic differences play certain roles in the distribution of IL-6 promoter polymorphisms because the distribution of the IL-6 -174 C allele is diverse among study subjects with different racial origins. Therefore, we examined IL-6 C-174G polymorphism in Taiwanese type 2 diabetic subjects to clarify the relationship of this polymorphism with Taiwanese type 2 diabetes mellitus in the context of the aforementioned mentioned contradictory results. All of our 101, type 2 diabetic patients and 112, non-diabetic, healthy individuals carried homologous G alleles. No C allele was found. Our study suggested that the C allele at the IL-6 -174 position was rare in Taiwanese people. Furthermore, our results demonstrated that IL-6 C-174G polymorphism is unlikely to play a role in the development of Taiwanese type 2 diabetes, regardless of its protective or promoting role.     

脂联素基因单核苷酸多态性与Ⅱ型糖尿病合并肥胖及胰岛素抵抗相关联

脂联素是近年新发现的脂肪组织特异性的细胞因子,其mRNA是脂肪组织中含量最丰富的基因转录产物,该因子可通过多种途径影响个体对胰岛素的敏感性。脂联素基因多态性与肥胖、胰岛素抵抗和2型糖尿病密切相关,而与冠心病相关性研究的报道较少。本研究以中国汉族人群1,098例为对象,其中304例冠心病(CHD)患者,389例糖尿病患者(T2DM),及405例性别年龄相匹配的正常对照,采用PCR-RFLP技术对脂联素基因-4522C/T进行基因分型,并分别对血脂水平、胰岛素抵抗、体重指数等临床数据进行分析比较。研究结果显示,脂联素基因-4522C/T各基因型及等位基因在CHD组与对照组、T2DM组与对照组中的分布差异无显著性;经分组分析发现,T2DM合并肥胖患者BMI≥25kg/m2TT基因型及T等位基因明显多于对照组,差异有显著性,P=0.014和P=0.034;TT基因型T2DM患者胰岛素抵抗指数(HOMA-IR)显著高于携带有C等位基因的T2DM患者,P=0.0069。本研究提示脂联素基因-4522C/T与中国汉族人群T2DM合并肥胖的发生及T2DM患者胰岛素抵抗相关,是引发糖尿病患者肥胖和胰岛素抵抗的重要候选基因,而与冠心病的发生无关联。     

Insulin sensitivity is not affected by mutation of codon 972 of the human IRS-1 gene

We investigated the relationship of codon 972 polymorphism of the insulin receptor substrate-1 (IRS-1) gene with insulin resistance in the Japanese population. Among 130 patients with type-2 diabetes mellitus (DM), we identified 6 who were heterozygous for the Gly972Arg mutation. Among 144 healthy subjects, 6 were heterozygous and 1 was homozygous for the mutation. A hyperinsulinemic euglycemic clamp study was performed in 3 of 6 diabetic patients with the heterozygous Gly972Arg mutation and in 60 without it. Both groups showed almost the same levels of insulin sensitivity (glucose infusion rate, GIR = 50.2 +/- 3.0 vs. 51.3 +/- 12.1 micromol/kg/min). Similarly, there was no difference in insulin sensitivity between healthy subjects with and without the mutation using the homeostasis model assessment (HOMA index = 1.14 +/- 0.50 vs. 1.02 +/- 0.63). The frequency of the Gly972Arg allele was not increased in diabetic patients compared with control subjects even in aged (>50 years old) or obese (BMI >/=25) subjects. Among healthy subjects, we identified a 25-year-old male with the homozygous Gly972Arg allele. He was slightly obese (BMI = 25.5) but showed relatively high insulin sensitivity, almost equal to that of healthy subjects without the mutation (GIR = 67.2 vs. 71.8 +/- 22.0 micromol/kg/min). Because the GIR in healthy subjects was significantly higher compared with that in type-2 DM patients, we speculate that another genetic or environmental factor producing a more deleterious effect on insulin sensitivity may exist in diabetic patients. We conclude that this gene abnormality does not play a role in the pathogenesis of insulin resistance and type-2 DM.     

Arg753Gln Polymorphism of the Human Toll-like Receptor-2 Gene in Children with Recurrent Febrile Infections

Polymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined. The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and Arg753Gln polymorphism of the TLR-2 gene.     

Polymorphism of XRCC1 codon arg 399 Gln is associated with higher susceptibility to endometriosis

Endometriosis shows some characteristics of malignancy, including local invasion and aggressive spread to distant organs. The pathology of endometriosis may involve a complex interaction among genetic defects, DNA repairing defects and environmental factors. Since DNA repair capacity is closely related to the sustaining of the genomic stability, an XRCC1 Arg399Gln polymorphism was performed to evaluate the possible association with endometriosis in this paper. Recruited adult females were divided into two groups: endometriosis group (n = 141) and non-endometriosis group (n = 100). Genomic DNA was obtained from their peripheral leukocytes. DNA fragment coding XRCC1 Arg399Gln polymorphism was amplified by PCR and subsequently digested with MspI, and then the genotypes and allelic frequencies in both groups were compared. The genotype distribution and allelic frequency of XRCC1 Arg399Gln polymorphism was significantly different (P < 0.05). The partition of the "GG" homozygote in the patient group was greater than that in the control group, which means that for those people with more G allele, they will have higher risk for endometriosis. We concluded that XRCC1 Arg399Gln polymorphism is associated with higher susceptibility to endometriosis and XRCC1 Arg399Gln polymorphism might be a useful biomarker for endometriosis.     

Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure

Human soluble epoxide hydrolase (hsEH) has been shown to play a role in regulating blood pressure and inflammation. HsEH consists of an N-terminal phosphatase and a C-terminal epoxide hydrolase domain. In the present study, we examined the effects of polymorphisms in the hsEH gene on phosphatase activity, enzyme stability, and protein quaternary structure. The results showed that mutants Lys55Arg, Arg103Cys, Cys154Tyr, Arg287Gln, and the Arg103Cys/Arg287Gln (double mutant) have significantly lower phosphatase activity compared to the most frequent allele (MFA) of hsEH. In addition, the Lys55Arg, Arg103Cys, Cys154Tyr, Arg287Gln, and the double mutant have significantly lower kcat/Km values. The stabilities at 37 degrees C of purified Arg287Gln and Arg103Cys/Arg287Gln mutants were also significantly reduced compared to the MFA. HPLC size-exclusion studies showed that the MFA exists predominantly as a dimer. However, the Arg287Gln and Arg103Cys/Arg287Gln mutants show increased concentration of the monomer. We conclude that the Arg287Gln polymorphism disrupts putative intra- and inter-monomeric salt-bridges responsible for dimerization.     

A Strong Relationship Between Oral Squamous Cell Carcinoma and DNA Repair Genes

Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.     

XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by occupational chromium exposure

ABSTRACT: BACKGROUND: Occupational chromium exposure may induce DNA damage and lead to lung cancer and other work-related diseases. DNA repair gene polymorphisms, which may alter the efficiency of DNA repair, thus may contribute to genetic susceptibility of DNA damage. The aim of this study was to test the hypothesis that the genetic variations of 9 major DNA repair genes could modulate the hexavalent chromium (Cr (VI))-induced DNA damage. FINDINGS: The median (P25-P75) of Olive tail moment was 0.93 (0.58-1.79) for individuals carrying GG genotype of XRCC1 Arg399Gln (G/A), 0.73 (0.46-1.35) for GA heterozygote and 0.50 (0.43-0.93) for AA genotype. Significant difference was found among the subjects with three different genotypes (P = 0.048) after adjusting the confounding factors. The median of Olive tail moment of the subjects carrying A allele (the genotypes of AA and GA) was 0.66 (0.44-1.31), which was significantly lower than that of subjects with GG genotype (P = 0.043). The A allele conferred a significantly reduced risk of DNA damage with the OR of 0.39 (95% CI: 0.15-0.99, P = 0.048). No significant association was found between the XRCC1Arg194Trp, ERCC1 C8092A, ERCC5 His1104Asp, ERCC6 Gly399Asp, GSTP1 Ile105Val, OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln and DNA damage. CONCLUSION: The polymorphism of Arg399Gln in XRCC1 was associated with the Cr (VI)- induced DNA damage. XRCC1 Arg399Gln may serve as a genetic biomarker of susceptibility for Cr (VI)- induced DNA damage.     

Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual urogenital infections

We investigated the population prevalence of polymorphisms of Arg753Gln TLR2gene, and Asp299Gly, Thr399Ile TLR4 genes among people living in the Poltava region, as well as data communication polymorphisms with the presence of diseases caused by urogenital infections. The group of population control was a random sample of residents of the Poltava region (n = 299). The group of patients with urogenital diseases included 156 people. Genotyping of these groups TLR2 Arg753Gln polymorphism and the gene TLR4 Asp299Gly, Thr399Ile was performed using PCR and subsequent restriction analysis. Statistically significant association of allele A ofgene TLR2 (p = 0.0018) and allele G of gene TLR4 (p = 0.085) with the presence of urogenital diseases was confirmed.     

The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung

Defects in the repair and maintenance of DNA increase risk for cancer. X-ray cross-complementing group 1 protein (XRCC1) is involved with the repair of DNA single-strand breaks. A nucleotide substitution of guanine to adenine leading to a non-conservative amino acid change was identified in the XRCC1 gene at codon 399 (Arg/Gln). This change is associated with higher levels of aflatoxin B1-adducts and glycophorin A somatic mutations. A case-control study was conducted to test the hypothesis that the 399Gln allele is positively associated with risk for adenocarcinoma of the lung. XRCC1 genotypes were assessed at codon 399 in 172 cases of lung adenocarcinoma and 143 cancer-free controls. Two ethnic populations were represented, non-Hispanic White and Hispanic. The distribution of XRCC1 genotypes differed between cases and controls. Among cases, 47.7% were Arg/Arg, 35.5% were Arg/Gln, and 16.9% were Gln/Gln. Among controls, XRCC1 allele frequencies were 45.5% for Arg/Arg, 44.8% for Arg/Gln, and 9.8% for Gln/Gln. Logistic regression analysis was used to assess the association between lung adenocarcinoma and the G/G genotype relative to the A/A or A/G genotypes. In non-Hispanic White participants, the lung cancer risk associated with the G/G genotype increased significantly after adjustment for age (OR=2.81; 95% CI, 1.2-7.9; P=0.03) and increased further after adjustment for smoking (OR=3.25; 95% CI, 1.2-10.7; P=0.03). Among all groups, a significant association was found between the G/G homozygote and lung cancer (OR=2.45; 95% CI, 1.1-5.8; P=0.03) after adjustment for age, ethnicity, and smoking. This study links a functional polymorphism in the critical repair gene XRCC1 to risk for adenocarcinoma of the lung.     

Association of the -112A>C polymorphism of the uncoupling protein 1 gene with insulin resistance in Japanese individuals with type 2 diabetes

The -112A>C polymorphism (rs10011540) of the gene for uncoupling protein 1 (UCP1) has been associated with type 2 diabetes mellitus in Japanese individuals. The aim of the present study was to investigate the effects of this polymorphism, as well as the well-known -3826A>G polymorphism (rs1800592), on clinical characteristics of type 2 diabetes. We determined the genotypes of the two polymorphisms in 93 Japanese patients with type 2 diabetes. Intramyocellular lipid content and hepatic lipid content (HLC) were measured by magnetic resonance spectroscopy. No significant differences in age, sex, BMI, or HbA1c level were detected between type 2 diabetic patients with the -112C allele and those without it. However, homeostasis model assessment for insulin resistance (p=0.0089) and HLC (p=0.012) was significantly greater in patients with the -112C allele. We did not detect an association of the -3826A>G polymorphism (rs1800592) of UCP1 gene with any measured parameters. These results suggest that insulin resistance caused by the -112C allele influences the susceptibility to type 2 diabetes.     

Angiotensin-converting enzyme gene polymorphisms and T2DM in a case�Ccontrol association study of the Bahraini population

Bahrain has one of the highest incidence rates of type 2 diabetes mellitus (T2DM). Development of diabetic nephropathy (DN) as a complication was noticed in some patients while absent in others. This interesting observation raises the role of certain genetic risk factors for the development of DN. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with T2DM. While some patients have predisposition to DN in the population, others have negative association. The present case-control association study was designed to investigate the association of ACE I/D polymorphism in T2DM patients in Bahrain especially in those who developed DN. A total of 360 T2DM patients (110 with DN and 250 without DN) and 360 healthy (non-diabetic) age-matched subjects were recruited for this study for comparison. The presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was investigated using PCR-gel electrophoresis. The results show that the distribution of the homozygote DD genotype of the ACE gene was high among Bahraini T2DM patients compared to the healthy non-diabetic subjects. In addition, the distribution of the deletion (D) allele was high among Bahraini T2DM patients with DN when compared to the healthy non-diabetic subjects. However, there was no significant difference in the distribution of ACE I/D allele and genotypes between DN patients when compared to those T2DM patients without DN. The results obtained in this study are in closely agreement with some previous reports which show a strong association of ACE polymorphism with T2DM patients, yet not a risk factor for development of DN.     

Susceptibility of XPD and RAD51 genetic variants to carcinoma of urinary bladder in North Indian population

For the present study, two polymorphisms, xeroderma pigmentosum, complementation group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent genotype. In males, the XPD 751C (Gln) allele was found to be associated with a significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of rural areas showed a significantly increased risk with the XPD Gln allele (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a significantly increased risk toward bladder cancer. For RAD51 135G/C polymorphism, no significant difference was observed in the allelic and genotypic frequencies. Even after stratification, no significant association could be seen. After stratifying histopathologically, the RAD51 CC genotype was associted with decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99) and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD polymorphism may be a predisposing factor, but the same cannot be said for RAD51 gene polymorphism.