Risk conferred by tagged SNPs of AGT gene in causing susceptibility to essential hypertension

Introduction: AGT gene harbors several variants of which 21 are found to be in high linkage disequilibrium as per Hapmap database. Studies delineating the importance of these tagged SNPs are very limited and lacking from Indian population. In the present study, we evaluated the contribution of four tagged SNPs namely, g.6635G?>?A, g.6506G?>?A, g.12840G?>?A, and g.13828T?>?C at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to essential hypertension (EHT).

Methods: About 215 hypertensives and 230 normotensives were genotyped for selected tagged SNPs using PCR-RFLP method.

Results: Significant association was obtained for g.6635G?>?A and g.6506G?>?A polymorphisms wherein GG homozygotes for both the markers were at risk for developing the condition. g.13828T?>?C polymorphism specially, female heterozygotes (TC) were found to be at increased risk for EHT. Haplotype GGGC was found to have a significant protective effect (p?=?0.0059). Markers g.6506G?>?A and g.12840G?>?A resulted in the creation of new enhancer sites thereby affecting splicing process.

Conclusion: The present report is the first one in the literature showing general- and gender-specific association of g.6506G?>?A and g.13828T?>?C polymorphisms, respectively, with EHT. However, further studies for replication of present observations are warranted from other populations and other parts of India.     

Synergistic effects of gene polymorphisms of the renin–angiotensin–aldosterone system on essential hypertension in Kazakhs in Xinjiang

Objective: To assess the synergistic effects of gene polymorphisms of the renin–angiotensin–aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang. Methods: A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR). Results: In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G. Conclusions: There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 -344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively.     

A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Objective

In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population.

Methods

1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3′-untranslated region (UTR).

Results

The human ABCG1 −367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 −768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay.

Conclusions

The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.     

A PTPN22 promoter polymorphism −1123G>C is associated with RA pathogenesis in Chinese

The minor allele of the non-synonymous single nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene has now been unequivocally confirmed as conferring susceptibility to RA in population from Europe and America, but not in population from Asia. The aim of this study was to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in Chinese Hans of Guangdong province. Four hundred and ninety-four cases with RA and 496 healthy controls were randomly selected, their SNPs at position −1123G>C (rs2488457), +1858C>T (rs2476601), +788G>A (rs33996649), and rs1310182 were genotyped using PCR–RFLP, followed by agarose gel electrophoresis. +1858C>T (rs2476601) and +788G>A (rs33996649) are not polymorphic in Chinese Hans. Meanwhile, our result reveals that the degree of association between the promoter polymorphism, −1123G>C and RA, was analogous to that observed in Japanese reports (odds ratio [OR] = 1.517, 95% CI = [1.154–1.995], P = 0.003). Expression study also indicated a tendency for association between −1123G>C and PTPN22 gene expression. Our study underpins that the promoter polymorphism, −1123G/C, may be a causal SNP for RA in Asian.     

The Univariation and Multiple Linear Regression Analyses for Seventeen SNPs in Thirteen Cardiovascular Disease-Predisposing Genes and Blood Pressure in Chinese Han Males

Blood pressure (BP) is a complex trait regulated by the interaction among multiple physiologic regulatory systems, likely involving numerous genes that lead to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension is based on multiple genes with minor effects. To learn the association between 17 single nucleotide polymorphisms (SNPs) in 13 cardiovascular disease-predisposing genes and blood pressure of Han males, the 17 SNPs genotypes of 375 Han males were detected and analyzed with BaiO gene chip. The relationship between the SNPs and blood pressure was analyzed with variance analysis and multiple linear regression analysis. Variance analysis and/or multiple linear regression showed that: systolic blood pressure (SBP) was increasing with the elevation of year; AGT²³⁵M, ApoE^112,158E4, and SerpinA3^rs4934A were relative to the increase of SBP; AGT²³⁵M, ET-2⁹⁸⁵G, ApoC3³²⁰⁶T, and ApoE^112,158E4 may have had some relation with diastolic blood pressure (DBP) elevation; and ApoB^Xba?+?was associated with the increase of pulse pressure (PP). These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene–gene interactive model for future studies.     

High Risk for Essential Hypertension in Males Conferred by g.15241A>G Polymorphism in Intron 3 of AGT Gene

A total of 180 hypertensive and 188 normotensive subjects were studied for demographic features and for variations in exon 4 including exon–intron boundary of AGT gene using single-strand conformation polymorphism analysis. Sequencing of the samples showing mobility shift revealed a single-nucleotide polymorphism variant g.15241A>G in intron 3 of the gene. The polymorphism was consistent with Hardy–Weinberg equilibrium in both the cases and the controls. Although the genotype distribution and allele frequencies did not differ significantly in general, high risk was observed for males with G allele (OR = 2.08; 95% CI = 1.02–4.21; P = .04). Similar results were obtained when the genotypes were tested in dominant model wherein G allele carriers were found to be at twofold risk for developing essential hypertension (OR = 2.09; 95% CI = 0.99–4.41; P = 0.05). This report is the first one in the literature showing association of g.15241A>G polymorphism with a clinical condition.     

Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB: c.79G>A) Heterozygotes

Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnI ^Gγ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.     

Apoptosis-related Fas and FasL gene polymorphisms’ associations with knee osteoarthritis

To investigate the associations between Fas and FasL gene polymorphisms and susceptibility to knee osteoarthritis. Genomic DNA was obtained from 146 patients with knee osteoarthritis and 102 healthy controls. Genotype distributions and allelic frequencies of four polymorphisms of Fas (-670 G>A rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were compared between the groups. Thereafter, this association was investigated between patients and controls of the same sex. There were significant differences between patients with knee osteoarthritis and controls regarding the genotype distributions and allelic frequencies of Fas-1377 G>A polymorphism (P = 0.0001 and P = 0.005, respectively). The Fas-1377 GG genotype and G allele were significantly more frequent in patients with knee osteoarthritis than in controls. Genotype distributions and allelic frequencies of Fas-670 G>A, FasL-844 T>C, and FasL IVS2nt-124 A>G polymorphisms did not differ between the groups (P > 0.05). However, there were no significant differences between patients and controls of the same sex (P > 0.05). These findings suggest that the Fas-1377 G>A polymorphism in the Fas gene related with apoptosis may contribute to susceptibility to knee osteoarthritis in the Turkish population. There is a need for further studies to evaluate the role of apoptosis in large cohorts.     

The relationship between single nucleotide polymorphisms of the interleukin-10 gene promoter in systemic lupus erythematosus patients in Malaysia: a pilot study

Aim: Recent studies have shown that single nucleotide polymorphisms (SNPs) have been identified within the promoter of the human interleukin-10 (IL-10) gene may participate in the pathogenesis of systemic lupus erythematosus (SLE) and may be related to disease activity. This is a pilot study that investigated the allelic and genotype frequencies of three SNPs in the human IL-10 gene promoter [rs1800896 (position: –1082G > A), rs1800871 (position: –824C > T) and rs1800872 (position: –597C > A)] among Malaysian SLE patients and normal subjects. Methods: Blood was drawn from 44 SLE patients and 44 age- and sex-matched healthy control subjects for DNA extraction. The SNPs were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There was no significant difference in the genotype and allele frequencies between the SLE patients and control subjects. A statistically significant difference was detected in the haplotype frequencies between the patients and controls (P = 0.004). Conclusions: There is a significant difference in the haplotype frequencies between the SLE patients and controls; the SNPs in the human IL-10 gene promoter could play an important role in the pathogenesis of SLE.     

TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus

Three-prime repair exonucleases 1 and 2 (TREX1 and TREX2) play a role in the metabolism and clearance of DNA. The objective of this study was to confirm whether polymorphisms of TREX1 and TREX2 are associated with genetic susceptibility to systemic lupus erythematosus (SLE), and examine associations with autoantibodies (auto-Abs) in SLE. We investigated the genetic variants in 24 Korean individuals by direct sequencing. The genotype distributions of single-nucleotide polymorphisms (SNPs) and haplotypes were analyzed with multiple logistic regression models while controlling for covariates. We identified 12 and 5 SNPs of TREX1 and TREX2, of which −20260G>C, −389T>C, −381C>T, and +531C>T SNPs of TREX1; −23386G>C, −14703G>A, −7279C>T, and +1747C>T SNPs of TREX2; and each of three haplotypes were selected for larger scale genotyping (n = 1,053). No statistically significant association with the risk of SLE was observed in TREX1 and TREX2. TREX1 polymorphism −20260G>C showed protective effect on the production of anti-Ro Ab, and +531C>T in exon 16 and ht2 [G–T–C–T] showed also protective effect on the production of anti-dsDNA Ab, although the effect of +531C>T disappeared after multiple correction. An erratum to this article can be found at     

Molecular characterization of Portuguese patients with mucopolysaccharidosis type II shows evidence that the IDS gene is prone to splicing mutations

Summary Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease caused by a defect in the iduronate-2-sulfatase gene (IDS). Alternative splicing of the IDS gene can occur and the underlying regulatory mechanism may be rather complex. Nevertheless, little information is available on the role of variations at the IDS locus in the splicing process. Here we report that splice mutations at the IDS locus are an important source of MPS II pathogenicity, accounting for almost 56% of Portuguese cases. Among 16 unrelated Portuguese MPS II patients, 15 different mutations were identified: six intronic splice mutations (c.104−2AG, c.241−2A>G, c.241−1G>A, c.418+1G>A, c.880−8AG and c.1181−1G>C); two exonic splice mutations (c.1006G>lC and c.1122C>T); five missense mutations (D269V, D69V, D148N, R88C and P86L); one nonsense mutation (Q465Ter); one total IDS gene deletion; and one rearrangement involving a IDS gene inversion. Furthermore, nine of the 15 detected mutations affected the usual splicing pattern at the locus. Some of them are responsible for dramatic changes in the splicing mechanism. For example, the substitution mutation, c.418+1G>A, revealed the presence of an exonic sequence inside intron 3. Our study provides evidence that the IDS locus is prone to splicing mutations and that such susceptibility is particularly high in exon 3 and neighbouring regions. Consequently, mutation screening of the IDS gene cannot be restricted to gDNA examination. Unless cDNA analysis is also conducted, misclassifications as silent or missense mutations can be produced and even uncharacteristic splice-site mutations can be misinterpreted as classic splicing defects that may generate severe, unconventional splicing alterations. Communicating editor: Douglas Brooks Competing interests: None declared References to electronic databases. OMIM disorder/gene accession number: 309900. EC number 3.1.6.13. HUGO-approved gene symbol: IDS. GenBank Accession number: AH002847. Vega Gene ID: TTHUMG00000022615. Ensembl Gene ID: ENSG00000010404     

Two single nucleotide polymorphisms in ALOX15 are associated with risk of coronary artery disease in a Chinese Han population

Arachidonate 12/15-lipoxygenase (12/15-LOX) has been implicated in the pathogenesis of atherosclerosis, but with contradicting results. The aim of this study was to investigate the association of two polymorphisms in ALOX15 and the risk of coronary artery disease (CAD) in a Chinese Han population. A total of 519 unrelated CAD patients and 608 unrelated control subjects of the Chinese Han population were recruited in the case-control study. Two tagSNPs, rs7217186:T>C and rs2619112:G>A, were selected and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The carriers of the C allele (the CC homozygote and the CT heterozygote) of rs7217186:T>C and the carriers of the A allele (the AA homozygote and the GA heterozygote) of rs2619112:G>A displayed elevated odds ratios (ORs) for CAD compared with the TT homozygotes and GG homozygotes, respectively, after adjusting for other potential confounders including age, sex, body mass index, systolic blood pressure, diastolic blood pressure, glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and smoking status (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.335–7.665, P = 0.009 and adjusted OR = 3.5, 95% CI: 1.343–9.330, P = 0.011). In stratified analyses, after adjusting those aforementioned confounders, the CC and CT genotypes of rs7217186:T>C were associated with a greater risk of CAD in subjects <60 years (adjusted OR = 5.7, 95% CI: 1.557–21.097, P = 0.009) and in females (adjusted OR = 9.3, 95% CI: 1.048–82.213, P = 0.045). For rs2619112:G>A, subjects (<60 years) carrying the A allele had a greater risk of CAD than the GG homozygotes (adjusted OR = 4.9, 95% CI: 1.215–19.547, P = 0.025); the male carriers of A allele also had a greater risk (adjusted OR = 3.5, 95% CI: 1.136–11.006, P = 0.029). In summary, the present study shows that after adjustment for other confounding CAD factors, rs7217186:T>C and rs2619112:G>A of ALOX15 are associated with increased risk of CAD in this Chinese Han population.     

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population

Single-nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle-related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p < .05 and OR: 7.62, p = .049, respectively). Additionally, rs2681472 and rs1401982 were in linkage disequilibrium with rs11105378. This study identified two ATP2B1 SNPs associated with RHT in the Japanese population. rs1401982 was most closely associated with RHT, and major allele carriers of rs1401982 required significantly more antihypertensive medications. Analysis of ATP2B1 SNPs in patients with hypertension can help in early prediction of RHT and identification of high-risk patients who are more likely to require more antihypertensive medications.     

No significant association between genetic polymorphisms in the TNAP gene and ankylosing spondylitis in the Chinese Han population

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in tissue non-specific alkaline phosphatase (TNAP) with ankylosing spondylitis (AS) in the Chinese Han population. We carried out both case-control studies in two independent Chinese AS cohorts (Eastern Chinese, Southeastern Chinese) involving 353 AS patients and 514 unrelated healthy controls and family-based association study involving 57 pedigrees. Two TNAP intronic SNPs rs3767155 (G/A), and rs1780329 (G/T) and 1 exonic variant rs3738099 (A/G) were genotyped using direct DNA sequencing method. The results showed that there was no significant difference in allele, genotype or haplotype frequencies between the AS patients and the controls at the three SNPs in either case-control or family-based association study, which indicated that the TNAP gene was unlikely to play a major role in the susceptibility to AS in the Chinese Han population. Ning Cheng and Qing Cai contributed equally to this work.     

Interleukin 12B rs3212227 T > G polymorphism was associated with an increased risk of gastric cardiac adenocarcinoma in a Chinese population

Gastric cardiac adenocarcinoma (GCA) is one of common malignant tumors in the world. Multiple genes that play critical roles in inflammatory pathways probably are associated with GCA risk. We conducted a hospital‐based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C > T, IL9 rs31564 G > T, IL10 rs1800872 T > G, IL12A rs2243115 T > G, IL12B rs3212227 T > G, and IL13 rs1800925 C > T on the development of GCA. Two hundred and forty‐three GCA cases and 476 controls were recruited. Their genotypes were determined using a custom‐by‐design 48‐Plex SNPscan kit. IL12B rs3212227 T > G polymorphism was associated with the increased risk of GCA. However, there was no significant association between the other five SNPs and GCA risk. Stratified analyses indicated that the risk of GCA associated with the IL12B rs3212227 T > G polymorphism was evident among female patients and patients who never smoked or consumed alcoholic drinks. These findings indicated that functional polymorphism IL12B rs3212227 T > G might correlate with GCA risk. However, our results were obtained with a limited sample size; the power of our analysis was low. Larger studies are required to confirm the current findings.     

Association of the variants in AGT gene with modified drug response in Korean aspirin-intolerant asthma patients

The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P = 0.0009–0.002; P^corr = 0.02–0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P = 0.0003–0.0006; P^corr = 0.006–0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients.     

Association of a polymorphism in the lipin 1 gene with systolic blood pressure in men

BACKGROUND: Lipin 1 plays a role in abdominal obesity, insulin resistance, and hypertriglyceridemia. The gene is located at 2p25.1, a susceptibility locus for hypertension. We studied the association of tagging single-nucleotide polymorphisms (SNPs) in the lipin 1 (LPIN1) gene with hypertension and blood pressure. METHODS: Twelve tagging SNPs from the HapMap database were genotyped using Sequenom MassArray in 268 hypertensive subjects and 407 normotensive controls, of whom 268 matched the cases in age and sex. RESULTS: None of the tagging SNPs were found to be associated with hypertension after correcting for multiple testing, although carriers of the minor allele of rs10520097 had nominally lower odds for hypertension (P = 0.014). After excluding subjects who were on antihypertensive medications, the minor allele of rs10495584 was nominally associated with lower mean systolic and diastolic blood pressures in men (121.1 +/- 14.2 and 76.3 +/- 10.2 mm Hg vs. 127.4 +/- 15.2 and 80.1 +/- 10.5 mm Hg, P = 0.002 and 0.007, respectively), but not in women (P > 0.05). The association of rs10495584 with systolic blood pressure in men remained significant after correcting for multiple testing and adjustment for age, waist circumference, insulin resistance, triglyceride, and high-density lipoprotein (HDL) cholesterol (beta = -0.158, P = 0.005). An analysis of statistically similar SNPs (ssSNPs) in the regions surrounding rs10495584 suggested that its effect may be caused by its high linkage disequilibrium (LD) with the SNP, rs11524, in which the major allele forms an exonic splicing silencer sequence. CONCLUSION: Our study provides further evidence that lipin 1 may play a role in blood pressure regulation, especially in men.     

Interleukin 17A rs4711998 A>G polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population

Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer‐associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital‐based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 17A (IL17A) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom‐by‐design 48‐Plex SNPscan Kit. IL17A rs4711998 A>G polymorphism was associated with the decreased risk of ESCC. When the IL17A rs4711998 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly decreased risk for ESCC (AG vs. AA: adjusted odds ratio 0.72, 95% confidential interval 0.53–0.98, P = 0.039). However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated that a significantly decreased risk of ESCC associated with the IL17A rs4711998 A>G polymorphism was evident among younger patients and patients who never smoking or drinking. These findings indicated that functional polymorphism IL17A rs4711998 A>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size; the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm current findings.