Association study of TLR-9 polymorphisms and systemic lupus erythematosus in Northern Chinese Han population

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involving in its etiology. The toll-like receptor 9 (TLR9) gene has been reported to have important roles in the development and progression of SLE. We performed a case–control study to investigate the effects of 4 SNPs in the TLR9 gene in the development of SLE in Northern Chinese population.

Methods

Four SNPs including rs187084, rs5743836, rs352139 and rs352140 were genotyped using the SNaPshot® method. A group of 430 SLE patients were compared to 424 normal controls. Data were analyzed by SPSS 17.0 and HaploView v 4.1 software.

Results

The frequency distributions of SNP rs351240 and haplotype H2 (TGCT) and H3 (CATT) were found to differ significantly between patient and control groups (p < 0.05), while other SNPs and haplotypes showed no significant difference between the two cohorts (p > 0.05).

Conclusion

The results revealed that variations in the TLR9 gene are associated with SLE, indicating that TLR9 may play an important role in the pathogenesis of SLE in the northern Chinese Han population.     

Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.     

Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.     

Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of systemic lupus erythematosus (SLE) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236) gene polymorphism and the risk of SLE using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Thirteen reports were recruited into this meta-analysis for the association of VDR gene polymorphism with SLE susceptibility. In this meta-analysis for overall populations, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype, and ApaI aa genotype, were associated with the risk of SLE. In Asians, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE. In Africans, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype, ApaI A allele, AA genotype and aa genotype were associated with the risk of SLE. However, VDR BsmI, Fok1, ApaI and TaqI gene polymorphism were not associated with the risk of SLE in Caucasians. In conclusion, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE in overall populations, and in Asians, but these associations were not found in Caucasians. However, more studies should be conducted to confirm it.     

Genetic polymorphisms in MMP 2, 3 and 9 genes and the susceptibility of osteosarcoma in a Chinese Han population

Background: There are no data about the role of MMPs polymorphism in development of osteosarcoma.

Patients and methods: Two-hundred fifty-one patients with osteosarcoma and 251 healthy controls were included to investigate the association between the MMP2, 3, 9 polymorphisms and the risk of osteosarcoma.

Results: Compared with the MMP2 SNP rs243865 homozygote CC, The heterozygous CT genotype was associated with significantly increased risk for osteosarcoma (OR?=?1.86, 95% CI?=?1.18–4.22, p?=?0.014); the TT genotype was associated with increased risk for osteosarcoma (OR?=?1.92, 95% CI?=?1.21–3.52, p?=?0.028). However, the genotype and allele frequencies of MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were not significantly different.

Conclusion: MMP2 rs243865 genotype was associated with increased risk for development of osteosarcoma in Chinese Han population.     

Association study of ACE polymorphisms and systemic lupus erythematosus in Northern Chinese Han population

Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involving in its etiology. Angiotensin converting enzyme (ACE) gene was reported to have important roles in the development and progression of SLE. In this study, a case-control study was carried out to investigate the effects of seven SNPs and I/D in ACE gene in the development of SLE in Northern China. Seven SNPs including A5466C, T3892C, A240T, C1237T, G2215A, A2350G and C3409T were genotyped by PCR-RFLP method, and I/D was examined by agarose gel electrophoresis followed PCR directly. 314 SLE patients were compared to 320 normal controls in the study. Data were analyzed by SPSS 13.0 and HaploView software. The frequency distribution of SNP A2350G and Alu I/D and five haplotypes (AAAACCCI, AGAACCTD, AAAATCTI, TAAATTTI and TAAATCTI) were demonstrated to be different between case and control groups significantly. Whereas other SNPs and haplotypes had no differences in two cohorts. The results revealed that variations of ACE gene had association with SLE, which indicated ACE gene may play an important role in pathogenesis of SLE in Northern Chinese Han population.     

Association between polymorphisms in the promoter region of miR‐17‐92 cluster and systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR‐17‐92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR‐17‐92 was measured by quantitative real‐time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46‐0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46‐0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52‐0.92, P = .010, respectively). Haplotype analysis showed that C‐G‐G, C‐A‐A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17‐9.17, P < 0.001; OR=2.33, 95%CI, 1.44‐3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti‐dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24‐0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31‐0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR‐17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR‐17.     

Association of MASP2 levels and MASP2 gene polymorphisms with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. MASP2 is a mediator that plays an important role in complement system. As dysregulation of the complement system has been demonstrated to correlate with SLE pathogenesis, the role of MASP2 in lupus has not been widely discussed. In the present study, serum levels of MASP2 were evaluated in 61 lupus patients and 98 healthy controls by training cohort, and then a validation cohort including 100 lupus, 100 rheumatoid arthritis, 100 osteoarthritis, 100 gout, 44 Sjogren's syndrome, 41 ankylosing spondylitis patients confirmed the findings. Receiver operating characteristic (ROC) curve analysis determined the discriminatory capacity for serum MASP2. PCR methods tested the association of MASP2 gene polymorphisms (rs7548659, rs17409276, rs2273346, rs1782455 and rs6695096) and SLE risk. Impact of polymorphism on MASP2 serum levels was evaluated as well. Results showed that serum levels of MASP2 were significantly higher in lupus patients and correlated with some clinical, laboratory characteristics in the training cohort, and were much higher as compared to that in different rheumatic diseases patients in the validation cohort. Serum MASP2 showed a good diagnostic ability for lupus. Genotype frequencies and allele frequency of polymorphisms rs7548659, rs2273346 were strongly related to SLE risk, and genotypes of rs17409276, rs1782455, rs76695096 were significantly correlated with lupus genetic susceptibility. Interestingly, patients carrying GA genotype of rs17409276, TT, TC genotype of rs6695096 showed higher levels of serum MASP2. The findings suggested that MASP2 may be a potential disease marker for lupus, and correlate with SLE pathogenesis.     

Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population

Background: Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in cancer development and progression.

Patients and methods: A hospital-based case-control study including 201 patients with OSCC and 199 healthy controls was conducted. Seventeen single-nucleotide polymorphisms (SNPs) of GSN were investigated by Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology.

Results: Through comparison of the 17 SNPs on GSN gene between the two groups, SNP rs1078305 and rs10818524 were verified to be significantly associated with an increased risk of OSCC. For GSN rs1078305, the TT genotype was associated with increased risk for OSCC (OR?=?1.92, 95% CI?=?1.11–3.32, p?=?0.028). CT/TT variants were also associated with increased risk for OSCC compared to the CC genotype (OR?=?1.83, 95% CI?=?1.25–3.84, p?=?0.032).

Conclusion: The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population.     

Methyl-CpG binding domain 1 gene polymorphisms and lung cancer risk in a Chinese population

Polymorphisms of the methyl-CpG binding domain 1 (MBD1) gene may influence MBD1 activity on gene expression profiles, thereby modulating individual susceptibility to lung cancer. To test this hypothesis, we investigated the associations of four MBD1 polymorphisms and lung cancer risk in a Chinese population. Single locus analysis revealed significant associations between two polymorphisms (rs125555 and rs140689) and lung cancer risk (p=0.011 and p=0.005, respectively). Since the two polymorphisms were in linkage disequilibrium, further haplotype analyses were performed and revealed a significant association with lung cancer (global test p-value=0.0041). Our results suggested that MBD1 polymorphisms might be involved in the development of lung cancer. Validation of these findings in larger studies of other populations is needed.     

Association between polymorphisms in AXIN1 gene and atrial septal defect

Abstract

Context: AXIN1 is a central component of Wnt signalling pathway which is essential for embryonic development.

Objective: To investigate whether polymorphisms of AXIN1 contribute to ASD susceptibility.

Materials and methods: Three tag SNPs (rs12921862, rs370681 and rs1805105) in AXIN1 were genotyped in 208 ASD patients and 302 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a Chinese population.

Results: Significantly increased ASD risk was observed to be associated with the A allele of rs12921862 (p?<?0.0001, OR?=?3.096, 95% CI?=?2.037–4.717). Increased ASD risk was observed to be associated with rs370681 in a codominant (p?=?0.043, OR?=?1.52, 95% CI?=?1.04–2.22) and overdominant model (p?=?0.016, OR?=?1.57, 95% CI?=?1.08–2.27).

Conclusion: rs12921862 and rs370681 may contribute to ASD susceptibility.     

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta-analysis

Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 −69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.     

Gene polymorphisms and serum levels of TL1A in patients with rheumatoid arthritis

Recent findings showed elevated expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) in rheumatoid arthritis (RA) patients and arthritis mice. However, whether TL1A gene polymorphisms may correlate with RA susceptibility needs to be discussed. This case-control study was performed on 350 RA patients and 556 healthy subjects to identify TL1A genetic variants (rs3810936, rs6478109, and rs7848647) and their possible association with TL1A levels, susceptibility to and severity of RA. Odds ratio and 95% confidence interval were calculated to represent the correlation between TL1A polymorphisms and RA. The TL1A serum levels were evaluated. Results showed that frequencies of TC, TT + TC genotypes of rs3810936, rs7848647 in RA patients were significantly lower in RA patients compared with controls. Patients with C allele showed more severe disease course (disease activity index: erythrocyte sedimentation rate, rheumatoid factor) than in carriers of T allele. However, the allele or genotype frequencies of rs6478109 were not associated with RA. In addition, TL1A genetic variants conferred higher TL1A levels in RA patients compared with controls. In conclusion, these findings indicated an association between TL1A rs3810936, rs7848647 variation and the susceptibility of RA in a sample of Chinese individuals, and TL1A may correlate with severity of RA.     

Association analysis between MDR1 gene polymorphisms and risk of hepatocellular carcinoma in Chinese population

Objective: XRCC4 play a key role in nonhomologous end-joining repair pathway. Alterations in DNA repair gene have been shown to reduce DNA repair capacity thereby inflicting carcinogenesis.

Methods: In a hospital-based case-control study, 192 prostate cancer (PCa) and 224 healthy controls. They were genotyped for XRCC4 G-1394T (rs6869366), intron 3 (rs28360071) intron 7 (rs28360317) and intron 7 (rs1805377), polymorphisms using polymerase chain reaction–restriction fragment length polymorphism.

Result: Carriers of GG genotype of rs6869366 were at reduced risk. Del/Del of rs28360071 and 28360317 demonstrated increased risk. The haplotype analysis was observed to be associated with a significant increase in PCa risk. Combined genotype of rs6869366, rs28360071 and rs1805377 have shown significant risk with high Gleason grade.

Conclusion: Our results suggested that the variant genotype of XRCC4 rs28360071 and rs28360317 and haplotype analysis may be associated with PCa risk.     

DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Background: Schizophrenia, schizoaffective disorder, and bipolar illness are common psychological disorders with high heritability and variable phenotypes. The disrupted in schizophrenia 1 ( DISC1) gene, on chromosome 1q42, has an essential role in neurite outgrowth and cell signaling. The purpose of this study was to investigate the association of three single-nucleotide polymorphisms (SNPs; rs6675281, rs2255340, and rs2738864) with schizophrenia disorder. These three SNPs were chosen as they had been used in most of the previous studies. Methods: In a case-control study of Iranian population for the first time 778 blood samples were collected including, 402 schizophrenic patients and 376 healthy controls. Genomic DNA was extracted from peripheral blood using DNA extraction kit (BioFlux Co). The genotypes of rs6675281, rs2255340, and rs2738864 were detected by nested allele-specific multiplex polymersae chain reaction (PCR). Results: Our data revealed that the three SNPs are significantly associated with schizophrenia (rs2255349 C>T: confidence interval (CI), 2.115 to 3.268; P = 0.0000 OR: 2.629; rs2738864 C>T: CI, 1.538 to 2.339; P = 0.0000 OR: 1.897; rs6675281 C>T: CI, 2.788 to 4.662; P = 0.0009241 OR: 3.605). Through applying the expectation-maximization (EM) algorithm, we calculated the haplotype frequency, and finally performed haplotype analysis with Bonferroni correction and data preprocessing methods and the results showed rs66875281 to have the highest association. Discussion: Our findings primarily showed that DISC1 gene polymorphisms contribute to schizophrenia risk and have a significant association with this disorder among Iranian population. The strategy was found to be easy, rapid, specific, and consistent for the co-occurring detection of the DISC1 polymorphisms. We could finally confirm that the polymorphisms are related to schizophrenia studied in Iranian population.     

Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single‐nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health‐related quality of life (HRQoL) was also measured by SF‐36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (P_BH = 0.039), and this association was more pronounced in the female subgroup (P_BH = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role‐emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.     

Association of single nucleotide polymorphisms of CACNA1A gene in migraine

INTRODUCTION:

Migraine is a chronic, neurovascular polygenic disease where genetic and environmental factors are involved in its etiology. Dysfunction of neuronal ion transportation can provide a model for predisposition for common forms of migraine. Mutations in genes encoding ion channels disturb the rhythmic function of exposed tissue that may also explain the episodic nature of migraine. Our aim was to study the single nucleotide polymorphisms of CACNA1A gene in migraine patients.

MATERIALS AND METHODS:

The subjects were the patients of migraine, in the age range of 18-80 years, diagnosed by a Neurologist, as per the diagnostic criteria of International Headache Society (IHS) Classification 2004 after excluding other causes of headache by clinical examination and relevant investigations.The controls were the age and sex matched healthy persons from the same population excluding the relatives of patients. Only those patients and the controls, who voluntarily participated in the study, were taken and their blood samples were taken for the study. Deoxyribonucleic acid (DNA) extraction was performed according to the manufacturer''s protocol for Qiagen DNA extraction kits (Qiagen, Hilden, NRW, Germany). DNA content was quantified by spectrophotometric absorption (Nanodrop Spectrophotometer, BioLab, Scoresby, VIC, Australia). Polymerase chain reaction was performed using an iCycler Thermal Cycler (Bio.Rad, Hercules, CA, USA). The polymorphic analysis of CACNA1A gene was carried out by two methods: Restriction fragment length polymorphism and sequencing.

RESULTS:

The study included a total of 25 patients of migraine, diagnosed on out-patient department basis as per IHS Classification 2004 and compared with age and sex matched 25 healthy controls. Most of the patients 23 (92%) were below the age of 50 years. 20 of the patients (80%) were females and 5 (20%) were males. The polymorphic analysis of CACNA1A gene revealed the presence of only the wild form of the gene for the codon E993V in both case and control groups.

CONCLUSION:

In our study, we could not find any polymorphism of CACNA1A gene in the selected patients. Instead the wild type of genotype was found in both patients and controls. This negative result presented here, implies that if the CACNA1A gene is involved in typical migraine (with and without aura), its contribution is very modest and therefore difficult to discern. Nevertheless, there are other genes that could be considered potential candidates for typical migraine susceptibility for which further research is needed.     

Association between XPG polymorphisms and stomach cancer susceptibility in a Chinese population

Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3′ terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital‐based case–control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03–1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13–2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non‐cardia stomach cancer. Further combined analysis indicated men, smokers, or non‐drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.