X-ray Cross-complementing Group 1 Gene Research Articles

Molecular Characterisation of X-ray Cross-complementing Group 1 (XRCC1) Gene and Risk Factors in Senile Cataract Patients attending a Tertiary Care Hospital, Uttar Pradesh, India

Introduction: Cataract arises because of aging of the crystalline lens of the eye which prevents clear vision. X-ray Cross-complementing Group 1 (XRCC1) is a Deoxyribonucleic Acid (DNA) repair protein which is involved in Single-Strand Breaks (SSBs) and Base Excision Repair (BER) pathway which is responsible for the efficient repair of DNA damage is mainly responsible for cataract in patients. Aim: To study the prevalence, risk factors and the molecular characterisation with its special association to XRCC1 gene in senile cataract patients. Materials and Methods: This was a cross-sectional study carried out in the Department of Anatomy and Ophthalmology, Rama Medical College Hospital and Research Centre, Kanpur, Uttar Pradesh, India, from April 2021 to April 2022. A total of 500 clinical patients were included in which 250 patients were confirmed as cataract positive patients. Venous blood of 5 mL was collected in Ethylene diamine tetra-acetic acid tubes. The DNA extraction for the detection of XRCC1gene was done using Qiagen DNA extraction kit as per manufactures guidelines, which was further confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: A total of 500 clinically suspected patients were included in which 250 cases were confirmed as cataract positive patients. The ratio of females was more (n=130, 52%) compared to males (n=120, 48%) with the mean age for females with 57.6% and for males with 61.13%. Hypertension (n=173, 69.2%) was the most common disease associated with the cataract patients. The ratio of males were more (n=91, 75.8%) compared to females (n=82, 63.07%). The mean age of males was 64.40 years and that of females were 62.45 years. The other co-morbidity included diabetes (48.8%), in which males constituted 67 (55.83%) participants compared to the females with 55 (42.3%) participants. The presence of XRCC1 gene was detected in all cataract positive patients, which was also confirmed by RT-PCR. Conclusion: The polymorphisms of DNA repair genes decreased their ability to repair DNA damage, leaving human body a greatly increased susceptibility to cancer or agerelated diseases. The association of XRCC1 gene with agerelated cataract susceptibility observed in the present study supports the view that XRCC1 gene plays an important role in susceptibility to age-related cataract, so early screening and its molecular profiling will help the clinician in the early diagnosis as well as early treatment.

Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer.

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

Polymorphism of XRCC1 Arg399Gln may predict for development of end-stage renal disease. A PCR confirmed case-control study

ObjectivesEvaluation of the frequency of X-ray Cross Complementing group 1 (XRCC1) Arg399Gln polymorphism among patients with end-stage renal disease (ESRD) patients and to determine if a possible association was present. Subjects & methodsBlood samples were obtained from 70 ESRD patients and 30 healthy volunteers as control group for routine laboratory investigations and genomic DNA was extracted using GeneJET Whole Blood DNA Purification Kit to detect XRCC1 codon 399 genotype Arg/Gln in exon 10. BCNL digestion resulted in two fragments of 389 and 121 bp for wild-type homozygous (Arg/Arg); one fragment of 510 bp for variant homozygous (Gln/Gln); and three fragments of 510, 389 and 121 bp for variant heterozygous (Arg/Gln). ResultsCompared to control subjects, ESRD patients showed significantly higher frequency of Arg/Gln genotype, but had significantly lower frequency of Arg/Arg genotype. Moreover, patients had significantly lower frequency of Arg allele in comparison to controls (57.1% vs. 83.3%, respectively). Furthermore, the frequency of recessive models; Gln/Gln + Arg/Gln was significantly higher, while the frequency of dominant models; Arg/Arg + Arg/Gln was non-significantly lower among patients than controls. Development of ESRD was positively correlated with the presence of XRCC1 Arg/Gln genotype, while was negatively correlated with the presence of XRCC1 Arg/Arg genotype. ROC curve analysis showed that presence of XRCC1 Arg/Arg genotype is a negative sensitive predictor, while XRCC1 Arg/Gln genotype is a positive significant predictor for development of ESRD and Regression analysis defined presence of XRCC1 Arg/Arg genotype as significant negative predictor for development of ESRD. ConclusionThe results of the current study indicated an intimate relation between XRCC1 gene polymorphism and development of ESRD and the predictive value of its presence for the possibility of progression of chronic kidney disease to ESRD stage.

The single nucleotide polymorphism arg399gln rs25487 in XRCC1 gene is a breast cancer risk factor, but is not related to tp53 mutation status

Genetic changes in DNA repair genes, such as X-ray cross-complementing group1 (XRCC1), can cause modifications in the capacity of damaged DNA repair and affect the risk of cancer. Several mutations in TP53, which is a tumor suppressor gene, have been associated with breast cancer. In this study, it is aimed to evaluate the association of genetic variation in XRCC1rs25487 single nucleotide polymorphism (SNP) with TP53 mutation and breast cancer risk. In this research, 200 breast cancer women and 200 controls from the Iranian-Azeri population, Iran, were enrolled. Genomic DNA was extracted from the whole blood of controls patients. PCR-RFLP was carried out to genotype all participants for XRCC1rs25487SNP. Determination of possible mutations of TP53 in exons 5,6,7, and 8 were performed on 30 cancerous breast tissues through sequencing the amplified fragments. Our results of the case-control study indicated that the GA genotype of XRCC1 gene in rs25487polymorphism has a significantly risk effect on the breast cancer in the dominant genetic model (OR: 1.580, 95% CI: (1.025-2.436); p-value =0.049) and also GA genotype of XRCC1 gene in rs25487polymorphism has a protective effect on breast cancer in overdominant genetic model (OR: 0.591, 95% CI (0.395-0.886), p-value = 0.014). Furthermore, genotypes of this SNP did not associate with the clinical specifications of the patients and P53 mutation status. Sequencing results showed the mutational spectrum of P53 in the studied cases. According to the results of this study, in some of the genetic models, XRCC1SNP appears to be a modulator of breast cancer risk in Iranian East-Azerbaijan women. However, there was no correlation between XRCC1SNP and TP53 mutation status of the tumor.

Role of DNA repair genes XRCC3 and XRCC1 in predisposition to type 2 diabetes mellitus and diabetic nephropathy

IntroductionIncreasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methodsPolymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusionPolymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14–8.40 and OR 3.29 95% CI 1.23–8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population.

Role of DNA repair genes XRCC3 and XRCC1 in predisposition to type 2 diabetes mellitus and diabetic nephropathy

IntroductionIncreasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methodsPolymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusionPolymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14–8.40 and OR 3.29 95% CI 1.23–8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population.

Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers

Surniyantoro HNE, Lusiyanti Y, Rahardjo T, Nurhayati S, Tetriana D. 2018. Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers. Biodiversitas 19: 1676-1682. This study was aimed to examine the association between XRCC1 exon 10 gene polymorphism and micronucleus frequencies in radiation workers and their relation to the confounding factors. This study involved 37 radiation workers and 37 controls from several hospitals in Indonesia. Genotyping of X-ray cross-complementing group 1 (XRCC1) exon 10 gene polymorphism and micronucleus assay were performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Cytokinesis-Block Micronucleus assay (CBMN assay), respectively. The results indicated that MN frequencies were not significantly higher in the exposed workers than in controls (20.46±6.42 versus 16.89 ±9.72; P=0.07). The micronucleus frequencies of radiation workers with mutant genotype showed not significantly higher than controls in the same genotypes (22±6.64 versus 11.75 ± 8.13; P=0.11). The confounding factors, like age, years of employment and equivalent doses were significantly associated with micronucleus frequencies (P<0.05). The equivalent dose has a significantly positive correlation with micronucleus frequencies among radiation workers, increasing the MN frequencies by 16.3 per 1 mSv of equivalent dose (P=0.001). The genetic polymorphism of XRCC1 gene exon 10 demonstrated no association with the extent of DNA damage in the hospital radiation workers. The MN frequencies were strongly associated with age, equivalent dose and years of employment.

Genetic Polymorphisms of X-ray Repair Cross-Complementing Group 1 and Apurinic/Apyrimidinic Endonuclease-1 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease is interspersed with exacerbations; periods of acute symptomatic, physiological, and functional deterioration. The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms and the risk of COPD. Blood samples from 354 unrelated subject (age range 18-60years; 156 with COPD, 198 healthy controls) were collected. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Asp148Glu using a confronting two pair primers polymerase chain reaction. GA genotype of XRCC1 gene was found to be predominant in the COPD group compared to controls with 1.86-fold increased risk for COPD (OR 1.86, 95% CI 1.20-2.88, p = 0.0013). TG genotype of APE1 was found to be predominant in COPD group compared to controls with the difference being statistically significant (OR 1.68, 95% CI 1.08-2.61, p = 0.0043). The GA haplotype was found to be predominant in COPD than controls with a 2.19-fold significant increase (OR 2.19, 95% CI 1.46-3.28, p = 0.003). Polymorphism in XRCC1 and APE1 gene is associated with an increased risk of COPD.

Association between XRCC1 polymorphisms and glioma risk among Chinese population.

The pathogenesis of glioma remains largely unknown now. It has been suggested that the X-ray cross-complementing group 1 (XRCC1) gene may influence the capacity to repair DNA damage leading to an increased gliomas susceptibility. This study aimed to evaluate the relationship between XRCC1 polymorphisms and glioma risk. Genotypes were assessed in 368 Chinese glioma patients and 346 healthy controls. XRCC1 Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487) and three additional polymorphisms were directly sequenced. The frequency of Arg280His A allele was significant lower in glioma group than in healthy controls [9.6 vs 16%, OR=0.60 (0.46-0.80), P<0.001]; the frequencies of GA or AA genotypes were different in two groups (16.6 vs 22.8%, 1.3 vs 4.7%). The frequency of Arg399Gln A allele was significant higher in glioma group than in healthy controls [38.7 vs 30.1%, OR=1.29 (1.11-1.49), P=0.001]; the frequencies of GA or AA genotypes were different in two groups (45.4 vs 38.2%, 16 vs 10.9%). This study demonstrates that the rs25489 (Arg280His) and Arg399Gln (rs25487) polymorphisms in XRCC1 gene might influence the risk of developing glioma in Chinese population.

Association Between XRCC1 Gene Polymorphisms and Risk of Glioma Development: A Meta-analysis

Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) gene polymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performed to provide a more accurate estimation. A computerized literature search of 5 electronic databases was conducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. A total of 11 studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and 2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriage was associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI 1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037- 1.684), whereas a marginal association was revealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown in the homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398- 2.945), no significant link was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, no significant association was found in each comparison. No particular study was found to significantly influence the pooled results, and no potential publication bias was detected. This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians, while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studies and the potential confounders, further studies are needed to confirm these results.

Functional polymorphisms in XRCC-1 and APE-1 contribute to increased apoptosis and risk of ulcerative colitis

The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms in apoptosis and the risk of ulcerative colitis (UC). Blood samples from 384 unrelated subject (age range 18-65years; 171 with UC, 213 healthy controls) were collected after colonoscopy. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Asp148Glu using a confronting two-pair primers polymerase chain reaction. Apoptosis and intracellular reactive oxygen species (ROS) levels in peripheral blood mononuclear cells were measured using annexin-V and H(2)DCFDA assay, respectively. The frequency of genotype Arg399Gln (heterozygous) of XRCC1 gene was significantly higher in patients with UC than the controls (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.13-2.64; p=0.01). Similarly the genotypic frequency of APE1 Asp148Glu showed statistically significant incidence among UC subjects (OR 1.54; 95% CI 1.02-2.33; p=0.04). Polymorphism in XRCC1 Arg399Gln and APE1 Asp148Glu together considerably increased the risk of UC (OR 2.303; 95% CI 1.43-3.69; p=0.0007). ROS levels were high in UC subjects compared with controls (p=0.01). Polymorphisms in XRCC1 Arg399Gln and APE1 Asp148Glu significantly increased the rate of apoptosis and risk of ulcerative colitis.

Polymorphisms of the DNA Repair GenesXPDandXRCC1and the Risk of Age-Related Macular Degeneration

Oxidative stress seems to be an important factor in the development of age-related macular degeneration (AMD). The role of DNA repair mechanisms has also received attention recently in AMD pathogenesis. This case-control study was conducted to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD), codons 312 and 751, and x-ray cross-complementing group 1 (XRCC1), codons 194 and 399, in patients with AMD and in disease-free control subjects. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze XPD Asp312Asn and Lys751Gln and XRCC1 Arg194Trp and Arg399Gln in 120 patients with AMD (65 with dry type and 55 with wet type) and in age-matched 205 disease-free control subjects. Genotypic and allelic distributions of the polymorphisms were detected. For the XPD polymorphism, although the allele frequencies were not different between the patients and healthy control subjects, there was a significant difference between frequencies for the XPD751 Gln/Gln genotype in AMD patients (9%) and healthy control subjects (19%; P=0.02). The XPD751 Gln/Gln genotype seemed to have a protective effect against development of AMD (odds ratio, 0.41; 95% confidence interval, 0.19-0.88). Stratification by subtype of AMD revealed that the XPD751 Gln/Gln genotype was significantly lower only in the patients with dry type (P=0.02). These interactions remained nearly significant after Bonferroni correction (P<0.0125). Haplotype analysis for the two XPD polymorphisms revealed that the haplotype GC (312Asp-(751)Gln) was a protective haplotype against AMD. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the XRCC1 gene between the patients and the control subjects. Polymorphism in XPD codon 751 may be associated with the development of AMD.

The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer

To evaluate the effect of excision repair cross-complementing group 1 (ERCC1) and X-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcome in patients receiving oxaliplatin-based regimens for metastatic colorectal cancer. Hundred and thirteen patients with a diagnosis of metastatic colorectal cancer were treated with oxaliplatin-based chemotherapy. ERCC1 codon 118C/T and XRCC1 codon 399A/G polymorphisms were tested by real-time polymerase chain reaction (RT-PCR) method in peripheral blood lymphocytes of these patients. Disease control rates and survivals were compared by types of genotypes. Analyses of the patterns of the polymorphism located at ERCC1 codon 118 showed that 55 (48.67%) patients were homozygous for C/C genotype, 15 (13.27%) were homozygous for the T/T genotype, and 43 (38.06%) were heterozygous for C/T genotype. Analyses of the polymorphism located at XRCC1 codon 399 showed that 61 (53.98%) patients were homozygous for A/A genotype, 13 (11.50%) were homozygous for the G/G genotype, and 39 (34.52%) were heterozygous for A/G genotype. After two cycles of chemotherapy, there was complete response (CR) in 1 patient, partial response (PR) in 24 patients, and stable disease (SD) in 56 patients. Altogether in 81 (71.68%) patients the disease was controlled after chemotherapy. Thirty-two (28.32%) patients showed disease progression. After adjusting for some clinical factors, both the ERCC1 polymorphism and the XRCC1 polymorphism lost their roles in predicting DCR (P = 0.662, P = 0.631) and MST (P = 0.692, P = 0.572). But the combination of ERCC1 and XRCC1 polymorphisms was significantly associated with DCR (P = 0.01) and MST (P = 0.000) independently. This is the first study which showed that polymorphisms of ERCC1 and XRCC1, in combination not individually, were independent predictors for DCR and OS. This may contribute to the selection of patients who would benefit from oxaliplatin-based chemotherapy for metastatic colorectal cancer.

Gastric Cardia Carcinoma is Associated with the Promoter -77T>C Gene Polymorphism of X-Ray Cross-Complementing Group 1 (XRCC1)

PurposeX-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the bas-excision repair pathway. Several single-nucleotide polymorphisms in the XRCC1 gene are identified and related with increased cancer risk development. In particular, the -77T>C polymorphism located on the promoter region relates with lung cancer risk development. The aim of this study is to analyze the -77T>C allelic frequencies in a population composed of 456 primary gastric cancer patients (GC) and 507 blood donor controls. MethodsGC patients were observed at the University of Siena, Italy; clinicopathological data and family history were available for the cancer group. The control group is composed of blood donors. Constitutional genomic DNA was PCR amplified, and XRCC1 -77T>C was detected using restriction enzyme BsrB I and analyzed in a 3% agarose gel. ResultsThe -77C>C homozygous genotype was significantly associated with increased risk of gastric cardia carcinoma (p = 0.023) with an odds ratio of 1.65 (95% confidence interval 1.14 to 2.4). In the family history stratification, we report a significant association (p = 0.043) between the -77T>C polymorphism and GC cases with familial lung cancer aggregation. ConclusionsOur results suggest that the XRCC1 -77T>C polymorphism is a relevant host susceptibility factor for gastric cardia cancer development and specific subsets of familial clustering of GC.

Polymorphisms of DNA repair genes XPD and XRCC1 and risk of cataract development

The association between oxidative or ultraviolet (UV) light induced DNA damage in the lens epithelium and the development of lens opacities, and the existence of DNA repair in lens epithelial cells have been reported. Polymorphisms of DNA repair enzymes may affect repair efficiency. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD) codon 751 and X-ray cross-complementing group 1 (XRCC1) codon 399, in a sample of Turkish patients with maturity onset cataract. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we analysed XRCC1-Arg399Gln and XPD-Lys751Gln polymorphisms in 195 patients with cataract (75 patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30 with mixed type) and in 194 otherwise healthy control group of similar age. There was a significant difference between frequencies for XPD-751 Gln/Gln genotype in cataract patients (12%) and healthy controls (20%) ( P = 0.008, OR = 0.40, 95% CI = 0.20–0.81). After stratification by the cataract subtypes, XPD-751 Gln/Gln genotype was found to be significantly different in patients with cortical (4%) type cataract in respect to control subjects (20%) ( P = 0.038, OR = 0.16, 95% CI = 0.04–0.64). In addition, the allele frequency of the C (Gln)-allele of XPD-Lys751Gln was found to be significantly different in mixed type cataract group ( P = 0.008, OR = 0.48, 95% CI: 0.26–0.90). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in XRCC1 gene between the groups. These findings suggest that polymorphism in XPD codon 751 may be associated with the development of maturity onset cataract.

The Association of XRCC1 Haplotypes and Chromosomal Damage Levels in Peripheral Blood Lymphocyte among Coke-Oven Workers

Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.