Association between myeloperoxidase polymorphisms and its plasma levels with severity of coronary artery disease

ObjectivesMyeloperoxidase (MPO) polymorphism ?463 has been related to higher cardiovascular risk. This study was conducted to test whether the MPO promoter polymorphism ?463A/G and MPO plasma levels are associated with coronary artery disease (CAD) severity.Design and methodsPatients submitted to elective coronariography were enrolled, CAD severity was assessed and blood samples collected to identify the MPO polymorphism and its plasma levels.ResultsGenotypes were determined in 118 patients. Among these patients, 12 (10%) were homozygous for AA, 69 (58%) for GG and 37 (32%) were heterozygous. Mean MPO plasma levels were 8.6 ± 4.7 ng/mL for AA, 8.6 ± 7.0 ng/mL for AG and 9.4 ± 5.6 ng/mL for GG genotypes. The CAD severity was not associated with MPO genotypes (p = 0.43), however, patients with higher CAD score presented higher MPO levels (p = 0.02).ConclusionWe found no association between MPO polymorphism and CAD severity, although a relation was observed for MPO plasma levels and extension of CAD.     

Functional vascular endothelial growth factor gene polymorphisms and diabetes: Effect on coronary collaterals in patients with significant coronary artery disease

BackgroundVascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. This study tested the association between functional VEGF + 405 C > G (rs2010963), ? 2578C > A (rs699947) polymorphisms, and coronary collaterals in patients with coronary artery disease (CAD).MethodThe collateral scoring system developed by Rentrop was used to classify 393 patients according to their collaterals as either “poor” (grades 0 and 1) or “good” (grades 2 and 3). Gene polymorphisms were analyzed by TaqMan assay.ResultsThe frequency of + 405C and ? 2578A alleles was higher in the good collaterals group (p = 0.007 and 0.005, respectively). For the + 405C > G allele, the odds ratio (OR) of good collaterals for CC to GG genotype was 2.54 (p = 0.003). For the ? 2578A allele, the OR of good collaterals for AA to CC genotype was 2.31 (p = 0.038). Univariate and logistic regression analysis found 2 polymorphisms in the additive model for associations with collateral development: + 405C > G (p = 0.005 and 0.010) and ? 2578C > A (p = 0.006 and 0.006). The VEGF + 405C > G polymorphism and DM revealed an interactive effect on collateral development (p = 0.027).ConclusionsThe VEGF + 405C > G and ? 2578C > A polymorphisms might be novel genetic factors affecting collateral development in Chinese patients.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

The association between miR-146a gene rs2910164 polymorphism and gastric cancer risk: A meta-analysis

PurposeStudies have demonstrated that single nucleotide polymorphisms (SNPs) in miRNAs may lead to varying functional outcomes by altering miRNAs expression, even leading to the development of cancers. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to gastric cancer has been studied during the recent years, but the results are still inconclusive and inconsistent. We performed a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphism and the risk of gastric cancer.Materials and methodsThe databases of PubMed, MEDLINE and Web of Science were searched for suitable studies. A total of 8 published case–control studies on miR-146a rs2910164 polymorphism and gastric cancer risk including 4308 cases and 6370 controls were included.ResultsOverall, significant association was observed between rs2910164 and gastric cancer risk in allele model (OR = 1.11, 95% CI = 1.02–1.21); homozygote model (OR = 1.26, 95% CI = 1.10–1.43) and dominant model (OR = 1.21, 95% CI = 1.09–1.34). Stratified analysis by ethnicity showed significant association between rs2910164 polymorphism and gastric cancer susceptibility in Asians (OR = 1.10, 95% CI = 1.00–1.23 for G vs. C; OR = 1.25, 95% CI = 1.09–1.43 for GG vs. CC; OR = 1.19, 95% CI = 1.07–1.33 for GG vs. GC+CC, respectively). When stratified by genotyping methods and sample size, increased gastric cancer risk was only observed with the method by TaqMan and the sample size more than 1000.ConclusionIn summary, this meta-analysis indicated that miR-146a rs2910164 polymorphism was associated with the susceptibility to gastric cancer, especially in Asian population.     

SIRT1 variants are associated with aging in a healthy Han Chinese population

BackgroundAging is influenced by diverse environmental and genetic risk factors. The SIRT1 (silent information regulator 1) gene has been shown to regulate lifespan and aging in previous studies. We determined whether variation in the SIRT1 gene is associated with aging in healthy Chinese population.MethodsThe study population comprised 482 healthy, unrelated Chinese subjects, of which 246 were aging individuals from 60 to 91 years old, and 236 younger individuals from 35 and 59 years old. All subjects were from Shenyang, China. Two single-nucleotide polymorphisms (SNP) were analyzed: rs3758391 near the 5′ end of the SIRT1 gene; and rs4746720, in the 3′ untranslated region.ResultsDifferences in allele and genotype frequency were seen between the groups, with rs3758391/C more common than rs3758391/T in the aging subjects (odds ratio = 1.453, p = 0.026), and with rs3758391/CC more common than rs3758391/CT and rs3758391/TT in the aging subjects (odds ratio = 3.042, p = 0.027). For the 3′ SNP, rs4746720/C was more common than rs4746720/T in the aging subjects (odds ratio = 1.347, p = 0.022), and rs4746720/CC was more common than rs4746720/CT and rs4746720/CT in the aging subjects (odds ratio = 1.461, p = 0.049). The haplotype frequency distribution was also different, with haplotype CC more common in the older group (odds ratio = 1.63, p = 0.01).ConclusionThese results suggest that SIRT1 gene polymorphisms may add a new factor on the multifactorial genetic contributions to aging.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

The −351A/G polymorphism of ESR1 is associated with risk of myocardial infarction but not with extreme longevity

BackgroundWomen live longer than men. Some possible reasons for this advantage are the protection provided by high concentrations of 17β-estradiol (E2) during the premenopausal period and polymorphic variants of the estrogen receptors (ERs), which mediate various cardiovascular functions of E2.MethodsWe tested whether the ?351A/G and ?397T/C polymorphisms of the ERα-encoding ESR1 were associated with extreme longevity. The genomic DNA of 148 centenarians (C), 414 young controls (Y), and 208 myocardial infarction patients (MI) was analyzed by RFLP-PCR.ResultsBoth polymorphisms were equally distributed in the Y, C, and in centenarians never diagnosed with MI (HC). In centenarians, none of these polymorphisms was associated with a particular lipid profile. The AA genotype of the ?351A/G polymorphism was less frequent in the C, HC and Y groups than in MI patients (p = 0.058, p = 0.021, and p = 0.004, respectively). In MI patients, the GG genotype of the ?351A/G polymorphism was associated with significantly lower mean total cholesterol, LDL, and HDL levels compared to the AG (p = 0.0194, p = 0.0213, and p = 0.0367, respectively) and AA genotypes (p = 0.0014, p = 0.0078, and p = 0.0448, respectively).ConclusionsThe ?351A/G ESR1 polymorphism might be associated with MI, but not with extreme longevity.     

Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

BackgroundGlutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer.MethodsWe first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs.ResultsAmong five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037), intronic SNP 3828599 (OR = 0.68, P = 0.025), and 3′ UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′ = 0.91).ConclusionsThe reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.     

RAD51 gene is associated with advanced age-related macular degeneration in Chinese population

ObjectivesThis study aims to investigate whether variations in RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of age-related macular degeneration (AMD) in Chinese population.Design and methodsA total of 119 Chinese patients with AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot.ResultsRs10483810 in RAD51 was significantly associated with advanced AMD (P = 0.045). Compared with the wild-type genotype GG, the odds ratio for the risk of advanced AMD was 4.92 (95% confidence interval: 1.04–23.36) for the heterozygous TG genotype. Moreover, the GT genotype at rs10483810 confers significantly increased risk of bilateral AMD compared to unilateral AMD (OR = 12.04, 95% CI: 2.50–57.69, P = 0.002). Rs13278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and rs9542236 in B3GALTL were not found to be associated with AMD (all P > 0.05).ConclusionOur data suggested that the risk allele T of rs10483810 in RAD51 gene is associated with an increased risk of advanced AMD, especially bilateral AMD, in Chinese population.     

MUC1 568 A/G genotype-dependent Cancer Antigen 15-3 levels in breast cancer patients

ObjectivesCA 15-3 is a widely used tumor marker for breast cancer. We have investigated whether the MUC1 568 A/G polymorphism can influence CA 15-3 levels in healthy women and patients with breast tumors.Design and methodsCA 15-3 was measured in 208 healthy women, in 67 with benign disease, and in 162 women with breast cancer. All subjects were genotyped for the MUC1 568 A/G polymorphism.ResultsSignificant differences were observed between mean CA 15-3 levels of control subjects grouped according to the MUC1 568 genotype (mean ± SD): AA (10.3 ± 3.8), AG (15.9 ± 5.0) and GG (19.0 ± 5.6) U/mL, p < 0.0001. Similar (median) results were observed in women with benign breast disease: AA (10.2), AG (14.2) and GG (16.6) U/mL, p < 0.0001, and those with breast cancer: AA (10.4), AG (17.1) and GG (23.9) U/mL, p < 0.0001.ConclusionsThe MUC1 568 A/G polymorphism strongly influences CA 15-3 levels in healthy women and women with either benign or malignant breast tumors.     

Receptor for advanced glycation end products (RAGE) and glyoxalase I gene polymorphisms in pathological pregnancy

ObjectivesThe aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy.Design and methodsPolymorphisms of RAGE gene (? 429 T/C, ? 374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy.ResultsNo differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p = 0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r = ? 0.536, p = 0.05).ConclusionsWe did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.     

Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

BackgroundImpaired ubiquitin–proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD).MethodsWe conducted a case–control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD.ResultsNo significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls ≥ 60 years of age (P = 0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals ≥ 60 years of age (OR = 0.61; 95% CI = 0.41–0.90, P = 0.010). This is also true for T allele (OR = 0.64; 95% CI = 0.44–0.91, P = 0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR = 0.42; 95% CI = 0.22–0.81, P = 0.009) and UCHL1 C-carrying genotype (OR = 0.67; 95% CI = 0.47–0.97, P = 0.032).ConclusionsOur results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people ≥ 60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.     

Association of angiotensin-converting enzyme polymorphism with coronary artery disease in Iranian patients with unipolar depression

ObjectivesMajor depressive disorder (MDD) is an increasingly recognized risk factor of coronary artery disease (CAD). The aim of this study was to assess the relationship between renin-angiotensin system (RAS) genetic polymorphisms and CAD in a sample of depressed Iranian patients.Design and methodsA total of 191 patients with a history of unipolar depression were enrolled in a case/control study. The presence of MDD was reconfirmed at study entry using DSM-IV criteria and CAD was diagnosed by coronary angiography. Genotyping of six RAS genes polymorphisms was performed by a modified PCR-RFLP method.ResultsDD genotype of ACE I/D was independently associated with the incidence of CAD in depressed patients (P = 0.011, OR = 9.41, 95% CI: 1.68–17.81). Moreover, serum creatinine (P = 0.033, OR = 11.91, 95%CI: 7.23–15.62) was an independent predictor of CAD among depressed individuals.ConclusionACE I/D polymorphism may play a major role in the development of CAD amongst Iranian depressed patients.     

Polymorphisms of the NOS3 gene in Southern Chilean subjects with coronary artery disease and controls

BackgroundNitric oxide (NO) from the endothelium, produced by oxidation of l-arginine to l-citruline for the action at the endothelial nitric oxide synthase (eNOS) is considered an important atheroprotective factor. The 894G>T, ? 786T>C and 4a/4b polymorphic variants of the NOS3 gene have been implicated in the development of coronary artery disease (CAD). We investigated the association between occurrence of CAD documented by angiography and the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 gene in Southern Chilean individuals.MethodsA total of 112 unrelated patients with diagnosis of CAD confirmed by angiography and 112 controls were included in this study. The 894G>T and ? 786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a/4b polymorphism just for PCR.ResultsThe genotype distribution and the relative allelic frequencies for the 3 variants investigated were not significantly different between CAD and control subjects (p = NS). Moreover, the odds ratio for CAD associated with the 894T (OR = 1.22, 95% CI 0.76–1.95), ? 786C (OR = 1.16, 95% CI 0.75–1.80) and 4a (OR = 0.97, 95% CI 0.48–1.95) variants failed to reach statistical significance.ConclusionThese findings suggest that the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 were not associated with CAD in the studied subjects.     

Evaluation of apolipoprotein M as a biomarker of coronary artery disease

ObjectiveTo investigate the possible role of apolipoprotein M (ApoM) in the development of coronary artery disease (CAD).Design and methodsCase-controlled study, which consisted of 118 CAD patients and 255 unrelated subjects used as control group. Plasma concentration of ApoM was determined by dot blot, severity of CAD was expressed with Gensini score or the numbers of lesioned coronary arteries, and serum lipid levels were also measured.Results and discussionOur study shows the mean level of plasma ApoM is 1.3757 ± 0.1493 ODu mm^? 2 in CAD patients, while it is 1.3502 ± 0.1288 ODu mm^? 2 in control group, and there are significant differences in plasma level of ApoM between two groups (t = 0.032, P < 0.05). Concentration of plasma ApoM is positively associated with plasma total cholesterol (r = 0.38, P = 0.025), high density lipoprotein cholesterol (r = 0.29, P = 0.03), low density lipoprotein cholesterol (r = 0.16, P = 0.03) and apolipoproein A–I (r = 0.24, P = 0.03). Multiple logistic and linear regression analysis showed that plasma concentration of ApoM did not correlate either with the number of lesioned coronaries or the Gensini score after adjusted for conventional cardiovascular risk factors (P > 0.05, respectively).ConclusionThe findings suggest that ApoM could not be an independent risk factor but a biomarker of CAD.     

Programmed death-1 (PD-1) polymorphisms in Chinese patients with esophageal cancer

ObjectivesEsophageal cancer is an extremely aggressive gastrointestinal malignancy, which appears to result from a complex interplay between genetic and environmental agents. The genetic loci conferring susceptibility have yet to be fully defined. Considering the role of programmed death-1 (PD-1) in immune regulation and tumor pathogenesis, we genotyped three functional single nucleotide polymorphisms (SNPs) in PD-1 in a Chinese population to explore whether these three SNPs confer susceptibility to esophageal cancer.Design and methodsA total of 629 new diagnosed esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this hospital-based case–control study. Genotyping was performed by the polymerase chain reaction–ligase detection reaction (PCR–LDR) method in all the subjects.ResultsIn the recessive model, when the PD-1 rs10204525 AA/AG genotypes were used as the reference group, the GG homozygote genotype was associated with a borderline statistically decreased risk of ESCC [adjusted odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.45–1.03, P = 0.067]. However, there were no significant associations between the other two SNPs and ESCC risk. Stratified analyses showed that a significantly decreased risk of ESCC associated with PD-1 rs10204525 A > G polymorphism was overt among male and younger patients.ConclusionsOur results demonstrate for the first time that the PD-1 rs10204525 polymorphism might contribute to susceptibility of ESCC and may therefore support the hypothesis that genetic variants, influencing T cell activity-associated gene regulation, may modify cancer risk.