Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

Association between interluekin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population

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 χ² test, there was significantly difference in the genotype distribution of IL-17A rs2275913 between cervical cancer patients and control subjects (χ²=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.     

IL-17F 基因多态性与类风湿关节炎发病风险关系的Meta 分析

目的:探讨白介素17F(IL-17F)基因多态性rs763780 和rs2397084 与类风湿关节炎(RA)易感性的关系。方法:计算机检索中国学术期刊全文数据库、万方数据库、中国生物医学文献数据库、Pubmed、Embase 以及Web of Science 中已发表的与RA 和IL-17F 基因多态性相关文献,进行Meta 分析。结果:纳入的5 项研究共收集RA 患者1 174 例(其中rs763780 含1 174 例,rs2397084 含985 例),正常对照966 例(rs763780 含966 例,rs2397084 含766 例)。Meta 分析结果显示,rs763780 与RA 密切相关(C vs.T:OR=1.74,95%CI =1.01-2.98,P =0.04;CC vs.TT:OR=3.17,95% CI =1.21-8.35,P =0.02;CT vs.TT:OR=1.80,95%CI =1.21-2.66,P =0.004;CC+CT vs.TT:OR=1.96,95% CI =1.35-2.83,P<0.001;CC vs.CT+ TT:OR=2.97,95%CI =1.13-2.66,P =0.03)。根据人种进行亚组分析发现,在欧洲人群中rs763780 与RA 密切相关,差异具有统计学意义。未发现rs2397084 与RA 之间的相关性。结论:IL-17F rs763780 是RA 的危险因素,IL-17F rs2397084 与RA 易感性是否有关仍不明确。     

Interleukin-17A rs2275913, Interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis

There are no reports about the association of interleukin (IL)-17A and IL-17F gene polymorphism and susceptibility to pediatric systemic lupus erythematosus (pSLE). Objective: To examine the possible role of IL-17A rs2275913, IL-17F rs763780 and rs2397084 polymorphisms as risk factors for pSLE in a cohort of Egyptian children and to investigate their association with the clinico-pathological features including lupus nephritis (LN). Methods: Typing of IL-17A and IL-17F polymorphisms was done using restriction fragment length polymorphism for 115 children with SLE and 259 age- and sex-matched healthy controls. Results: No significant differences were found between pSLE patients and healthy controls for the allele and genotype frequencies of IL-17A rs2275913, IL-17F rs763780 and rs2397084 (p?>?0.05). However, the combined genotype GGAGAA and the haplotype GGA had significant association with pSLE (p_c?=?0.042 and <0.001, respectively). The AA genotype of IL-17F rs763780 is more frequent in female patients (p?=?0.002) and the AA genotype of IL-17F rs2397084 is more associated with positivity of ds-DNA (p?=?0.007). No more associations were found for the demographic and clinical data of pSLE patients including risk of LN development, risk of non-remission, overall survival, activity and chronicity indices. Conclusion: The GGAGAA combined genotype and the GGA haplotype of IL-17A rs2275913, IL-17F rs763780 and rs2397084 can be considered risk factors for the development of SLE in Egyptian children. IL-17A rs2275913, IL-17F rs763780 and rs2397084 are not related to the LN development, SLE disease activity or overall survival.     

Interleukin-17A and -17F single nucleotide polymorphisms associate with susceptibility of asthma in Chinese Han population

Interleukin 17 (IL-17) plays important roles in the progression of asthma. Genetic variants in the Il-17 may influence the immunopathogenesis of many diseases. Many studies have investigated the relevance of IL-17 polymorphism with cancers or immune diseases, including asthma. In this study, single nucleotide polymorphisms (SNPs) of IL-17 were explored by PCR-RFLP and verified by sequencing method. The frequencies of genotypes and alleles were analyzed. Haplotypes were analyzed with the SHEsis online program. The relationship between the genotypes of SNPs and IgE level was also investigated. The False Discovery Rate (FDR) correction was performed (P-adjusted?<?0.05). The frequencies of A allele, GA and (GA?+?AA) genotype of rs3748067 were significantly higher in asthma patients. As for rs763780, the C allele in patients was more frequent than healthy controls. In addition, we found C carriers (CT?+?CC) were significantly higher in asthma patients. We further found that the haplotype CT for IL-17F (rs763780/rs2397084) was associated with an increased susceptibility of asthma, but this association did not survive after FDR correction. The level of serum total IgE in mutant group (GA?+?AA) of rs3748067 was significantly higher than the wild genotype (GG) group and control group. These results suggested that IL-17 SNPs, but not haplotypes may be associated with the susceptibility of asthma in Chinese Han population from central China.     

Association between interleukin-17 gene polymorphisms and risk of coronary artery disease

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.     

Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis

We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.     

Impact of the IL-17F,IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806?G/A and IL-23R (rs1884444?G/T, rs10489629?G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR– RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR?=?3.947; p?=?0.001 and OR?=?3.538; p?=?0.002, respectively). Frequencies of the rs1884444 TT genotype (OR?=?138.1) and the rs1884444 T allele (OR?=?2.176) were also higher in SLE patients (both p?0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r² – 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p?0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444?G/T (D'-0.199, r² –0.026). The genotype–phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p?=?0.01), the IL-17F rs763780 and age (p?=?0.008) and lupus anticoagulant (p?=?0.09), the IL-23 rs11171806 and urea (p?=?0.08) and C3 complement (p?=?0.03), and the IL-23R rs1884444?G/T and activated partial thromboplastin time (p?=?0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444?G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.     

Analysis of IL-17 gene polymorphisms in Chinese patients with dilated cardiomyopathy

Cardiomyopathy is one of the major causes of sudden death and/or progressive heart failure. Dilated cardiomyopathy (DCM), comprising 60% of the cases of identified cardiomyopathy, is the most common form of heart muscle disease. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been implicated in the pathogenesis of various diseases. To evaluate the influence of IL-17A and IL-17F gene polymorphisms on the risk of DCM, a case-control study was conducted in a Chinese Han population. The TaqMan® SNP Genotyping Assay was used to genotype the SNP rs2275913 of IL-17A and SNP rs763780 of IL-17F in 288 DCM patients and 421 ethnicity-matched controls. No significant difference in genotypic and allelic frequencies between DCM patients and control subjects was observed. However, Results of stratified analysis revealed that rs763780 was associated with male DCM patients in a dominant genetic model (p = 0.031, OR = 1.83, 95% CI = 1.04–3.22). Our results suggest that the tested two IL-17 SNPs, rs2275913 and rs763780, are not found to be associated with DCM in the Chinese population studied.     

Association of single nucleotide polymorphisms in interleukin 12 (IL-12A and -B) with asthma in a Chinese population

Increasing evidence has indicated that genetic variants may contribute to immune dysregulation and susceptibility to noninfectious inflammatory diseases. Cytokines, including interleukin 12 (IL-12), play a key role in the regulation of the immune system. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) in IL-12A and IL-12B were associated with asthma in a Chinese population. Genotype characteristics were determined in 197 asthma patients and 369 controls by the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing assay. The genotype and allele frequencies of IL-12A rs568408 demonstrated significant differences between cases and controls (p < 0.001). The AC genotype of rs3212227 was associated with a significantly decreased risk of asthma compared with the AA genotype (p = 0.036). The subjects carrying combined genotypes (rs568408 AG and rs3212227 AC/CC) at both loci had a 2.05-fold increased asthma risk compared with those carrying all other genotypes (p = 0.001). In contrast, individuals carrying combined genotypes of rs568408 GG and rs3212227 AC/CC were associated with a significantly decreased risk of asthma compared with those carrying the combined genotypes of rs568408GG and rs3212227AA (p = 0.009). No significant difference was reported for rs2243115 between cases and controls. These results suggest that the SNPs in IL-12A rs568404 and IL-12B rs3212227 may individually and jointly contribute to the risk of asthma in a Chinese population.     

IL-10 基因多态性与溃疡性结肠炎易感性的关系及对临床预后的影响

目的:探讨IL-10 多态位点的基因多态性与溃疡性结肠炎的易感性及对临床预后的影响。方法:采用病例对照研究设计,选取80例溃疡性结肠炎患者作为病例组,另外选性别和年龄匹配的健康受试者作为对照组。所有患者治疗前抽取空腹静脉血并提取DNA,设计819 T/ C(rs1800871)、592A/C(rs1800872)、 -1082 G/ A(rs1800896)PCR 引物进行PCR 扩增,扩增产物酶切后进行琼脂糖凝胶电泳以确定基因类型,采用Logistic 回归计算校正相对危险度(OR)和95% 置信区间(95%CI)评价基因多态性与溃疡性结肠炎的易感性,并分析对临床预后的影响。结果:(1) 病例组患者IL鄄10 多态位点rs1800896 基因类型AA、GG 和AG 分布频率与对照组受试者差异具有统计学意义(P<0.01);(2)与rs1800896 基因型AA 比较,基因型为GG 的患者溃疡性结肠炎危险性显著升高(P<0.01),并且临床缓解率显著降低(P<0.01);(3)病例组患者IL-10多态位点rs1800871 基因类型CC、CT 和TT 分布频率与对照组受试者差异无统计学意义(P>0.05);(4)病例组患者IL鄄10 多态位点rs1800872 基因类型AA、AC 和CC 分布频率与对照组受试者差异无统计学意义(P>0.05)。结论:IL-10 多态位点rs1800896 基因类型GG 可增加溃疡性结肠炎的易感性,并且显著降低患者的临床预后。     

Association between matrix metalloproteinase gene polymorphisms and development of ischemic stroke

We investigated the association between MMP2 rs243865, MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and development of ischemic stroke in a Chinese population. Between January 2012 and May 2014, a total of 317 patients with ischemic stroke and 317 health control subjects were enrolled into our study. The MMP2 rs243865, MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals carrying with the CC genotype and the TC+CC genotype of MMP9 rs3918242 were associated with a significantly increased risk of ischemic stroke when compared with the TT genotype, and the ORs (95% CI) was 5.47 (2.64-12.38) and 1.55 (1.08-2.24), respectively. The TC+CC genotype of MMP9 rs3918242 was associated with an elevated risk of ischemic stroke in tobacco smokers, and the OR (95% CI) was 2.03 (1.11-3.74). In conclusion, our study suggests that MMP9 rs3918242 polymorphism is correlated with an elevated risk of ischemic stroke, and this gene polymorphism has interaction with tobacco smoking in the risk of ischemic stroke.     

Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: A meta-analysis

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR = 1.61, 95% CI = 1.17–2.23, P = 0.004); A allele was significantly associated with increased GC risk compared with G allele (OR = 1.22, 95% CI = 1.06–1.41, P = 0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR = 1.40, 95% CI = 1.04–1.88, P = 0.025; CT vs. TT: OR = 1.35, 95% CI = 1.16–1.58, P < 0.001; C allele vs. T allele: OR = 1.30, 95% CI = 1.15–1.47, P < 0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis.     

Association between Interleukin-10 gene polymorphisms and risk of early-onset preeclampsia

We conducted a case-control study to investigate the role of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) polymorphisms in the development of early-onset preeclampsia. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the polymorphisms of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872). The genotype distributions of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) confirmed with HWE in the controls, and the P value for HWE was 0.41, 0.38 and 0.26, respectively. The results of the multivariate logistic regression analysis revealed that the association of individuals expressing the CC genotype and AC+CC of IL-10 -592A/C (rs1800872) with a significantly increased risk of early-onset preeclampsia in co-dominant and dominant models, compared to the AA genotype; the OR (95% CI) for these individuals was determined to be 2.09 (1.12-3.90) and 1.66 (1.03-2.71), respectively. In the recessive model, we found that CC genotype of IL-10 -592A/C (rs1800872) was associated with the increased risk of early-onset preeclampsia when compared with AA+AC genotype (OR = 1.67; 95% CI = 1.01-2.92). In conclusion, our study has indicated that IL-10 -592A/C (rs1800872) polymorphism was associated with an increased risk of early-onset preeclampsia in a Chinese population.     

Association of four common SNPs in microRNA polymorphisms with the risk of hepatocellular carcinoma

We conducted a case-control study to investigate genetic variants of miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832 and miR-499 rs3746444 in the development of HCC in a Chinese population. This case-control study included 266 HCC patients and 266 control subjects between January 2012 and December 2013. Conditional logistical regression analysis indicated that TT genotype and T allele of miR-196a2 rs11614913 carried a 2.29-fold (95% CI = 1.30-4.05) and 1.60-fold (95% CI = 1.11-2.32) increased risk of HCC when compared with CC genotype, respectively. The subgroup analysis indicated that the effect of miR-196a2 rs11614913 polymorphism was influence by HBV infection. HBV infection subjects carrying the CT + TT genotype of miR-196a2 rs11614913 had an increased risk of HCC, and the OR (95% CI) was 2.89 (1.19-7.02). In conclusion, miR-196a2 rs11614913 polymorphism may contribute to identifying individuals, especially in HBV-infected subjects, who are at high risk for HCC.     

Genetic polymorphisms of interleukin 17A and interleukin 17F and their association with inflammatory bowel disease in a Chinese Han population

Objective

Interleukin-17A and interleukin-17F (IL-17A and IL-17F) are candidate genes for chronic inflammatory disease. We investigated the association between IL17A/F gene polymorphisms and susceptibility to and clinical features of inflammatory bowel disease (IBD).

Methods

A total of 270 ulcerative colitis (UC) patients, 82 Crohn’s disease (CD) patients and 268 healthy controls were recruited in this study. Genomic DNA was extracted and analyzed for IL17A/F gene polymorphisms using ligase detection reaction allelic technology.

Results

Compared to the controls, the mutant allele C for IL17F rs763780 was significantly more common in CD patients [14.0 vs 8.4 %, P = 0.033, odds ratio (OR) 1.18, 95 % confidence interval (CI) 1.41–3.04] and was associated with the disease lesion location. This variant of IL17F rs763780 also had a weak correlation with the age of UC onset (P = 0.05, OR 0.97, 95 % CI 0.94–1.00). The IL17A (rs2275913, G-197A) variant had a weak association with the severity of disease: patients with the mutant allele A tended to suffer mild active UC. The haplotype (GGTT) of IL17A formed with four single nucleotide polymorphisms (rs2275913, rs8193037, rs8193038, and rs3804513) was associated with an increased risk of UC (P = 0.034, OR 4.58, 95 % CI 1.54–13.64).

Conclusions

The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD. The IL17A (rs2275913, G-197A) variant had a weak association with the severity of UC. There was a risk haplotype in IL17A which could increase the risk of UC.     

GATA3-IL-13 通路基因多态性和IL-13 水平与哮喘病的相关性研究

目的:哮喘是一种慢性炎症性呼吸道疾病,有数据表明GATA3-IL-13 基因参与哮喘病的生物学理论是可信的。本研究目标是调查哮喘患者中GATA3-IL13 通路基因的多态性与IL-13 水平的关系,评估在新疆人口中GATA3-IL-13 基因多态性与IL-13 水平的相关性。方法:279 例哮喘患者和277 例对照组(健康人)通过MassARRAY SNP 分型系统进行分析,通过ELISA 法检测IL-13 的水平,运SPSS22.0 和Graph Pad Prism 6.0 软件进行数据统计和分析。结果:哮喘组IL-13 水平中(rs2066960 AA),GATA3(rs3781093 CC)基因型与CC (rs2066960)、TT (rs3781093)相比具有增加患病的风险(P<0.05)。同样的,IL-13(rs2066960) C-A 等位基因具有增加哮喘患病的风险(P<0.05)。而rs3781093 C-T 等位基因没有显著性差异(P>0.05)。结论:哮喘组GATA3(rs3781093)风险性位点发现与哮喘病相关,rs2066960 等位基因的C-A 突变与血清中IL-13水平的表达有关。     

白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。     

Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population

We systematically analyzed the association of nine SNPs of seven key NER pathway genes with the development of laryngeal cancer patients, and investigated whether NER pathway polymorphisms could serve as potential biomarkers for laryngeal cancer risk. 271 patients with pathologically proven laryngeal cancer and 271 control subjects were included in our study. Genotyping of ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs50871, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs2094258, XPA rs2808668 and XPC rs2228001 were analyzed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying the TT genotype of ERCC1 rs11615 were correlated with an increased risk of larynx cancer when compared with the CC genotype (OR=1.89, 95% CI=1.07-3.37; P value=0.02). Moreover, individuals with the GG genotype of ERCC2 rs50871 were associated with an elevated risk of larynx cancer when compare with the TT genotype (OR=2.03, 95% CI=1.15-3.63; P value=0.01). We found a significant interaction between ERCC2 rs50871 polymorphism and tobacco smoking in the risk of larynx cancer (P for interaction <0.05). In conclusion, our study showed that ERCC1 rs11615 and ERCC2 rs50871 polymorphisms could influence the risk of larynx cancer in Chinese population, particularly among smokers.     

Association of interleukin-17A and -17F gene single-nucleotide polymorphisms with autoimmune thyroid diseases

Th17 lymphocyte and its relative cytokines have been shown to play an important role in autoimmune thyroid diseases (AITD). The aim of this study was to investigate the association between IL-17A and IL-17F gene polymorphisms and two main types of AITD, Graves' disease (GD) and Hashimoto's thyroiditis (HT). Whole blood specimens and clinical data were collected from 508 AITD patients (326 with GD and 182 with HT) and 224 age- and gender-matched healthy controls, respectively. IL-17A (rs2275913, rs8193037, rs3819025) polymorphism was determined using DNA sequencing method and IL-17F/rs763780 polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR -RFLP). The results indicated that the frequencies of IL-17F/rs763780 genotypes in patients with GD and HT differed significantly from their controls (P = 0.013 and P = 0.005, respectively); the G allele frequencies were also significantly higher in the patient groups than the control groups (P = 0.002 and 0.001, respectively). For IL-17A/rs2275913 and rs8193037 SNP, no significant difference was observed in patients with either GD or HT compared to the control groups (P>0.05). Interestingly, for rs3819025, the frequency of A allele was lower in patients with GD than controls (P = 0.011). The frequencies of haplotype AGGG and GGGG in patients with GD and HT were significantly higher than in controls (P = 0.012, P = 0.019, P = 0.017 and P = 0.029, respectively). In conclusion, the results indicate that IL-17F/rs763780 polymorphisms may affect the susceptibility to AITD, and IL-17A/rs3819025 SNP is likely a protective factor to GD in the Chinese population.