Genetic polymorphisms of IL17A and pri-microRNA-938, targeting IL17A 3'-UTR, influence susceptibility to gastric cancer

We report an association between gastric cancer (GC) and polymorphisms in IL17A, rs2275913 (-197 G > A), rs3748067 (*1249 C > T), and pri-miR-938, rs2505901 (T > C). We employed the multiplex PCR-SSCP method to detect gene polymorphisms in 337 GC cases and 587 controls. The minor allele frequency of rs2275913 was significantly higher, and those of rs3748067 and rs2505901 significantly lower, in GC cases than controls. The rs2275913 AA homozygote was associated with an increased risk (OR, 2.38; 95%CI, 1.63-3.46; p < 0.0001) for the development of both intestinal and diffuse types of GC. The rs3748067 T polymorphism was associated with a decreased risk for intestinal GC (OR, 0.511; 95%CI, 0.272-0.962; p = 0.037), whereas rs2505901 C locus carried a decreased risk overall for GC (OR, 0.733; 95%CI, 0.545-0.985; p = 0.039). In addition, rs3748067 T allele was inversely correlated with lymph node metastasis. Our results suggest that polymorphisms in both IL17A and pri-miR-938 contribute to cancer risk susceptibility and therefore can affect the development of gastric cancer.     

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.     

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.     

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.     

Investigation of the relationship between IL17A,IL17F and ILR1N polymorphisms and COVID-19 severity: The predictive role of IL17A rs2275913 polymorphism in the clinical course of COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the mortality rate of the disease has been relatively under control as of 2022, more than 15 million confirmed COVID-19 cases have been detected in Turkey to date, causing more than 100,000 deaths. The clinical manifestation of the disease varies widely, ranging from asymptomatic to acute respiratory distress syndrome causing death. The immune response mechanisms have an important impact on the fine adjustment between healing and enhanced tissue damage. This study aims to investigate the relationship between the variants of the interleukin 1 receptor antagonist (IL1RN), interleukin 17A (IL17A), and interleukin 17F (IL17F) genes and COVID-19 severity. The study population comprised 202 confirmed COVID-19 cases divided into three groups according to severity. The IL1RN variable number of a tandem repeat (VNTR) polymorphism was genotyped by polymerase chain reaction (PCR), and IL17A rs2275913, IL17F rs763780 and rs2397084 polymorphisms were genotyped by the PCR-based restriction fragment length polymorphism method. Statistical analysis revealed a significant association between IL17A rs2275913 variant and COVID-19 severity. The AA genotype and the A allele of IL17A rs2275913 were found significant in the severe group. Additionally, we found a significant relationship between haplotype frequency distributions and severity of COVID-19 for the IL17F rs763780/rs2397084 (p = 0.044) and a combination of IL17F rs763780/rs2397084/ IL17A rs2275913 (p = 0.04). The CG and CGA haplotype frequencies were significantly higher in the severe group. IL17A rs2275913, IL17F rs763780 and rs2397084 variants appear to have important effects on the immune response in COVID-19. In conclusion, variants of IL17A rs2275913, IL17F rs763780 and rs2397084 may be the predictive markers for the clinical course and potential immunomodulatory treatment options in COVID-19, a disease that has placed a significant burden on our country.     

Association of IL17 and IL23R gene polymorphisms with rheumatic heart disease in South Indian population

ABSTRACT

Background: IL-23/Th17 signaling pathway plays a crucial role in the cell-mediated immune response against bacterial infections and also in the pathogenesis of inflammatory and autoimmune diseases. Recent studies indicate that Th17 cell-associated cytokines are involved in the progression and maintenance of valvular lesions in rheumatic heart disease (RHD). Variants in the genes of cytokines that are potentially involved in Th17 response may influence interindividual differences in their expression levels, thereby contributing to the pathogenesis of immune-mediated diseases such as RHD.

Objective: The aim of the study is to investigate the association of IL17A, IL17F, and IL23R gene variants with the risk perception of RHD.

Methods: A total of 225 individuals (99 RHD patients and 126 healthy siblings) were recruited for the study. The IL17A (rs2275913), IL17F (rs763780), and IL23R (rs10889677) polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphisms and amplification-refractory mutation system-polymerase chain reaction methods, respectively.

Results: The frequency of IL17A (rs2275913) A/A genotype was significantly high in pooled RHD patients (odds ratio [OR] = 2.76; p_c = 0.021), rheumatic fever (RF) patients (OR = 14.5; p_c = 0.0001), and mitral valvular lesions patients (OR = 2.74; p_c = 0.039) when compared to healthy siblings. However, the IL17F (rs763780) and IL23R (rs10889677) polymorphisms did not show any association with RHD.

Conclusions: The results suggest that IL17A (rs2275913) polymorphism is associated with the development of RF/RHD in South Indian population. Further studies are required to substantiate the association of these genes with the disease risk.     

Role of gene polymorphisms/haplotypes and serum levels of interleukin-17A in susceptibility to viral myocarditis

Interleukin-17A (IL-17A) has been implicated in the pathogenesis of viral myocarditis (VMC). However, the role of IL-17A polymorphisms in susceptibility to VMC has not been reported to date. The aim of this study was to explore the association between IL-17A variants as well as serum IL-17 levels with VMC. Three single-nucleotide polymorphisms (SNPs) (rs2275913, rs3819025, and rs3748067) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in 236 VMC patients and 259 controls from China. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay kits. Multivariable logistic regression analysis that the rs2275913 AA genotype and the haplotype -197A/+45G/+1249G (AGG) were associated with an increased risk of VMC (all P?<?0.05). Consistent with these findings, the rs2275913 AA genotype was linked to higher serum IL-17A compared to GG/AG genotype (all P?<?0.001). We observed no associations between the other two SNPs and risk of VMC. Serum IL-17A levels were significantly higher in the VMC group than controls (P?<?0.001) and gradually increased with the increase of New York Heart Association grade in VMC patients (P?<?0.05). Spearman correlation test revealed that the serum IL-17A level was correlated with the cardiac damage and left ventricular systolic functions among VMC patients (all P?<?0.05). Our study reveals that IL-17A expression may contribute to the development and severity of VMC. The SNP rs2275913 in the IL-17A gene might exert influence on susceptibility to VMC via linking with the serum IL-17A level.     

Evaluation of IL17A expression and of IL17A,IL17F and IL23R gene polymorphisms in Brazilian individuals with periodontitis

The IL23/Th17 axis plays an important role in the pathogenesis of cell-mediated tissue damage caused either by autoimmunity or immune responses against bacterial infection. Single nucleotide polymorphisms in the IL17A, IL17F and IL23R genes have been associated with several inflammatory diseases. However, these polymorphisms have not yet been studied in periodontitis. The aim of present study was to evaluate the expression of IL17A and occurrence of the IL17A (rs2275913), IL17F (rs763780) and IL23R (rs11209026) gene polymorphisms in different clinical forms or severity of periodontitis in a sample of Brazilian individuals. Peripheral blood was obtained from 30 non-smoker individuals and analyzed by flow cytometry to determine IL-17 expression. Genomic DNA was obtained from oral swabs in 180 individuals and analyzed by Real-time PCR. The study group was composed by individuals without periodontitis (control), with aggressive periodontitis (AP) and with chronic periodontitis (CP). Higher frequency of IL17A+CD4+ T cells was observed in control group. The A+ genotype from IL17A (rs2275913) was associated with lack of disease. No association was found considering the IL17F and IL23R polymorphisms. Our data suggest that IL17A and the presence of IL17A (rs2275913) A allele are associated with the absence of periodontal disease.     

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.     

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.     

Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta-analyses were conducted to determine the associations between IL17A rs8193036 (−737C/T), rs2275913 (−197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta-analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR] = 1.490, 95% confidence interval [CI] = 1.027–2.161, p = .036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta-analysis. This meta-analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility.     

Polymorphisms in cytokine genes IL6, TNF,IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections

Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.     

StIL-17 gene polymorphisms in the development of pulmonary tuberculosis

We conduct a case-control study to explore the possible association between IL-17 gene polymorphisms and development of TB. Methods: The study population comprised 428 TB subjects and 428 control subjects between January 2013 and June 2014. Genotyping analyses of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 and rs9382084 were analyzed using polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). Results: The TB cases were more likely to have a habit of smoking when comparing with controls. By conditional logistic regression analysis, individuals carrying CC genotype of rs763780 were more likely to have a significantly increased risk of TB when compared with TT genotype. The OR (95% CI) for CC genotype of rs763780 was 2.98 (1.58-5.92). Conclusion: In conclusion, we suggest that rs763780 play a critical role in the etiology of TB. These findings could be helpful in identifying individuals at increased risk for developing TB.     

IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil

We evaluated the influence of the IL8 T‐738A (nonidentified rs), IL8 T‐353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single‐nucleotide polymorphisms on leprosy. The AA genotype of IL8 T‐353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age‐of‐onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1–13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1–5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age‐of‐onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.     

Associations of IFN-γ rs2430561 T/A,IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection：a meta-analysis

Several studies investigated associations of IFN-γ rs2430561 T/A,IL28 B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus（HBV） infection,but the results were controversial.Therefore,we performed a meta-analysis of all published observational studies to address this inconsistency.Literature was searched in online database and a systematic review was conducted based on the search results.A total of 24 studies were included and dichotomous data were presented as odds ratio（OR） with a 95%confidence interval（CI）.The rs2430561 T allele was associated with reduced persistent HBV infection risk（T vs.A：OR,0.690;95%CI,[0.490,0.971]）,while the rs2077647 T allele significantly increased the risk of persistent HBV infection（T vs.C：OR.1.678;95%CI,[1.212,2.3231）.Rs 2077647 CC might play a role in protecting individuals against HBV persistence（TT vs.CC：OR,4.109;95%CI,[2.609,6.473]）.Furthermore,carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype（TT vs.AA：OR,0.555;95%CI,[0.359,0.856]）.For rs12979860 C/T polymorphism,no significant correlation with HBV infection outcomes was found.In subgroup analyses,the results were similar to those of overall analysis.However,for rs2077647 TT vs.TC＋CC,significantly increased risks were observed in the Asian and hospital-based population,but not in the overall analysis.IFN-γrs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection,but no association was found between IL28 B rs12979860 C/T and HBV infection.     

JAK2 rs10758669 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-analysis

In this meta-analysis, we aimed to clarify the impact of Janus kinase 2 (JAK2) rs10758669 polymorphisms on ulcerative colitis (UC) and Crohn's disease (CD) risk. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 %CIs) were calculated. Eleven studies with 7009 CD patients, 7929 UC patients, and 19235 controls were included. The results showed that JAK2 rs10758669 polymorphism was associated with CD (AC vs. AA, OR?=?1.16, 95 %CI, 1.08–1.24; CC vs. AA, OR?=?1.29, 95 %CI, 1.17–1.43; AC?+?CC vs. AA, OR?=?1.19, 95 %CI, 1.11–1.27; CC vs. AA?+?AC, OR?=?1.19, 95 %CI, 1.09–1.31; C vs. A, OR?=?1.14, 95 %CI, 1.09–1.20) and UC susceptibility (AC vs. AA, OR?=?1.14, 95 %CI, 1.06–1.22; CC vs. AA, OR?=?1.33, 95 %CI, 1.20–1.47; AC?+?CC vs. AA, OR?=?1.18, 95 %CI, 1.10–1.27; CC vs. AA?+?AC, OR?=?1.24, 95 %CI, 1.12–1.36; C vs. A, OR?=?1.15, 95 %CI, 1.10–1.21). But no significant association was found between JAK2 rs10758669 polymorphism with CD in Asian. Either in adult-onset group or multi-age group, hospital-based group or population-based group, JAK2 rs10758669 polymorphism was associated with CD and UC susceptibility. This meta-analysis indicated that JAK2 rs10758669 polymorphism was a risk factor both for CD and UC, especially in Caucasian. The differences in age of onset and study design did not influence the associations obviously. Gene–gene and gene–environment interactions should be investigated in the future.     

Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11–4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25–3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).     

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.     

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

Association of AIRE Polymorphisms with Genetic Susceptibility to Rheumatoid Arthritis in a Chinese Population

Recently, genetic polymorphisms within the autoimmune regulator (AIRE) have been implicated in the genetic susceptibility to rheumatoid arthritis (RA) in Japanese and Spanish. The aim of this case–control study involving 232 patients with RA and 313 ethnically matched control subjects was to investigate the association of AIRE rs2075876 and rs760426 polymorphisms with genetic predisposition to RA in a Chinese population. The genotypes of AIRE rs2075876 and rs760426 polymorphisms were determined by SNaPshot assay. A significant difference in the allele frequency of AIRE rs2075876 polymorphism between cases and controls was detected (A versus G, OR 1.33, 95 %CI 1.04–1.69, P?=?0.02, P corrected (Bonferroni correction) Pc?=?0.04). Significant evidence was found for the association between the minor allele A of AIRE rs2075876 polymorphism and the risk of RA under the recessive model (AA versus AG?+?GG, P?=?7.15?×?10^?3, Pc?=?1.43?×?10^?2). The frequency of the minor allele G of AIRE rs760426 polymorphism was higher in patients compared with controls (47.8 % versus 42.1 %), and this deviation showed a trend towards significant level (P?=?0.06, Pc?=?0.12). The association between the minor allele G of AIRE rs760426 polymorphism with RA risk under the dominant model and the recessive model revealed that significant evidence was detected under the recessive model (GG versus GA?+?AA, P?=?0.02, Pc?=?0.04). Our results indicated that AIRE rs2075876 and rs760426 polymorphisms were involved in the genetic background of RA in the Chinese population.