Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer.
ABSTRACT: BACKGROUND: Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P?=?0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype A(rs2275913)G(rs3819025)G(rs3748067), located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P?=?0.0471 after correction for multiple testing). CONCLUSIONS AND SIGNIFICANCE: Our results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.
Project description:We conducted a study to analyze the association of three common SNPs of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 gene polymorphisms with the risk of cervical cancer in a Chinese population. Our study included 352 cervical cancer patients and 352 controls between January 2013 and December 2014. Genotyping of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 genes was performed by multiplex PCR assays using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). By χ(2) test, there was significantly difference in the genotype distribution of IL-17A rs2275913 between cervical cancer patients and control subjects (χ(2)=11.45, P=0.003). By conditional logistic regression analysis, we found that individuals with the GA and AA genotypes were associated with an increased risk of cervical cancer when compared with the GG genotype in codominant model, and the adjusted Ors (95% CI) were 1.57 (1.13-2.18) and 2.01 (1.15-3.49), respectively. In dominant model, we found that the GA+AA genotype of rs2275913 was correlated with a moderate increased risk of cervical cancer compared with the GG genotype (OR=1.64, 95% CI=1.20-2.24). We only found significant interaction between rs2275913 polymorphism and HPV-16 or 18 infection in the risk of cervical cancer (P for interaction <0.05). In conclusion, our study suggests that IL-17A rs2275913 polymorphism may affect the development of cervical cancer in codominant and dominant models, and this gene polymorphism has interaction with HPV-16 or 18 infection.
Project description:Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs.
Project description:We conducted a case-control study to estimate the association between IL-17A rs2275913, rs3819025 and rs3748067 polymorphisms and development of coronary artery disease. A total of 415 patients with coronary artery disease and 448 health controls were recruited during the period of March 2013 and October 2014. Genotyping of IL-17A rs2275913, rs3819025 and rs3748067 were analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism. By logistic regression analysis, we found that individuals with the AA genotype (OR, 2.18; 95% CI, 1.35-3.56) and the GA+AA genotype (OR, 1.39, 95% CI, 1.06-1.84) of rs2275913 were associated with an increased risk of coronary artery disease when compared with the GG genotype. Individuals carrying the GA+AA genotype of rs2275913 were more likely to have a higher risk of coronary artery disease in those with hypertension and smoking habit, and the adjusted ORs (95% CI) were 3.92 (2.13-6.82) and 2.74 (1.71-4.40). In conclusion, we suggest that individuals with the AA genotype and the GA+AA genotype of rs2275913 are associated with an increased risk of coronary artery disease, especially in those with hypertension and smoking habit.
Project description:A 1:1 matched case-control study was conducted to analyze the association between three common interleukin (IL)-17A and IL-17F single nucleotide polymorphisms (SNPs) and the risk of developing gastric cancer. Genotyping of SNPs rs2275913, rs763780 and rs3748067 within the IL-17 gene were detected by performing polymerase chain reaction-restriction fragment length polymorphism analysis. Gastric cancer patients were more likely to be cigarette smokers, alcohol drinkers and have a family history of cancer in their first-degree relatives. Patients carrying the rs763780 polymorphism were correlated with a significant increased risk of gastric cancer in codominant, dominant and recessive models. Additionally, individuals with the rs763780 polymorphism were correlated with a markedly increased risk of gastric cancer among alcohol drinkers in codominant, dominant and recessive models. Furthermore, a significant correlation was identified between the rs763780 polymorphism and the consumption of alcohol. However, no association was identified between rs2275913 and rs3748067 polymorphisms and the risk of developing gastric cancer. Thus, the present study reported that the rs763780 polymorphism may be associated with risk of developing gastric cancer in the population studied, particularly in alcohol drinkers.
Project description:Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.
Project description:The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population.We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C?>?T alleles on the expression of IL-17A.Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR?=?0.43, 95 % CI?=?0.23-0.83) and rs8193036 TT (adjusted OR?=?0.59, 95 % CI?=?0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI?=?0.13-0.86 for rs3748076; adjusted OR?=?0.41, 95 % CI?=?0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR?=?0.45, 95 % CI?=?0.21-0.98 for rs3748076; adjusted OR?=?0.46, 95 % CI?=?0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR?=?0.42, 95 % CI?=?0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C?>?T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study.The rs3748067 G?>?A and rs8193036 C?>?T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.
Project description:<h4>Objective</h4>Interleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case-control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity.<h4>Methods</h4>IL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed.<h4>Results</h4>RAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381-5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242-2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088-3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079-15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257-3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms.<h4>Conclusions</h4>IL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.
Project description:BACKGROUND:Knee osteoarthritis is a joint disease which is characterized by degeneration of articular cartilage and subsequent subchondral bone changes. Polymorphisms of IL-17A/F gene were the recognized candidate genes associated with knee osteoarthritis risk although the results were conflicting. The aim of this study was to determine whether IL-17A(rs2275913) and IL-17F(rs763780) polymorphisms confer susceptibility to knee osteoarthritis. METHOD:Literature search was performed in PubMed, Medline, Cochrane Library, Web of science, Embase, and Google Scholar (last search was updated on June 20, 2019), and assessing this association was performed by calculating odds ratios with 95% confidence intervals. Statistical heterogeneity was quantitatively evaluated by using the Q statistic with its p value and I2 statistic. RESULT:Six case-control based studies were included involving IL-17A(rs2275913) (2134 cases and 2306 controls) and IL-17F(rs763780) (2134 cases and 2426 controls). The overall analysis suggested that the A allele of the rs2275913 polymorphism, and the C allele of the rs763780 polymorphism in the IL-17 gene may increase the risk of OA. However, subgroup analysis revealed that no association between IL-17A(rs2275913) gene and knee OA risk was found in Caucasian population. CONCLUSIONS:This meta-analysis revealed that the IL-17A(rs2275913) gene polymorphisms may increase the risk of knee OA in Asians, and the IL-17F(rs763780) gene polymorphisms may increase the risk of knee OA both in Asians and Caucasians. However, because of the limitations of the present study, additional larger studies are needed to confirm our findings in the future.
Project description:Interleukin (IL)-17 have been reported to be associated with the pathogenesis of colorectal cancer (CRC). Few studies investigated the association between IL-17 gene polymorphisms and risk of CRC with inconsistent findings. Thus, we recruited 352 CRC cases and 433 controls in a Chinese population and their genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. Our data showed that IL-17A rs2275913 polymorphism was associated with the increased risk of CRC, while no association was observed for IL-17F rs763780 polymorphism. Stratified analyses revealed that the significant association was also obtained in the females, smokers, drinkers and age ? 60 years groups for rs2275913 polymorphism. Moreover, the CC and/or GC genotype of rs2275913 polymorphism were correlated with TNM stage and lymph node metastasis. No association was shown between IL-17F rs763780 polymorphism and clinical characteristics of CRC. In conclusion, our data indicate that IL-17A rs2275913 polymorphism but not IL-17F rs763780 polymorphism contributes to increased risk for CRC patients in this Chinese population.
Project description:Background:IL-17 expressed by Th17 cells play a crucial role in tissue inflammation by induction of proinflammatory and neutrophil mobilizing cytokines, and IL-17 polymorphisms are associated with colorectal cancer (CRC). Objective:We investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population. Materials and methods:The study included 117 diagnosed CRC patients and 100 age- and gender-matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C) single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were assessed. Results:We observed significant association between rs2275913 in IL-17A and susceptibility to CRC (p = 0.016228). The AG and AA genotypes conferred 2-fold and 2.8-fold, respectively, higher risk of developing CRC compared with individuals having GG genotype. Stratification of the data based on gender and age revealed very strong association of CRC with IL17A rs2275913 only in males and "AG" genotype in patients ?57 years of age at the time of disease diagnosis. The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL-17A mRNA expression in CRCs was significantly elevated compared to adjacent normal tissues, particularly in early stages of disease (p = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors. Conclusion:The IL-17A G197A variant may be utilized as a genetic screening marker in assessing CRC risk, and its expression can be used as a biomarker for early detection of CRC in the Saudi population.