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.     

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.     

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 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.     

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.     

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.     

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.     

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 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.     

The Polymorphism of IL-17 G-152A was Associated with Childhood Asthma and Bacterial Colonization of the Hypopharynx in Bronchiolitis

Objective

Interleukin (IL)-17 plays an important role in the pathogenesis of asthma. We investigated the association between single-nucleotide polymorphism (SNP) of IL-17 (rs2275913, IL-17 G-152A) and asthma-related traits. Its effect on IL-17 production was also attractive.

Methods

One hundred and sixty eight childhood asthmatic patients, 144 bronchiolitis patients, and 205 healthy controls were recruited in this study. SNP rs2275913 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. Peripheral blood mononuclear cells (PBMCs) from parts of healthy controls with different genotype were isolated and cultured with phytohaemagglutinin (PHA) for detection of IL-17 in the supernatants.

Results

SNP rs2275913 was associated with asthma (P?=?0.03) in genotype frequency test. Children with homozygous A were 2.29 times more likely to have asthma than others (95% confidence interval 1.39–3.78, P?=?0.001). The strength of associations was moderately higher by allergy comorbidity. Furthermore, SNP rs2275913 A allele was associated with abnormal lung function and serum total IgE in asthmatics, although the production of IL-17 by PHA-induced PBMC seemed to be not different among individuals with different genotypes. The distribution of SNP rs2275913 in bronchiolitis was marginally statistically different with controls and demonstrated a tendency close to that in asthma. Higher Streptococcus pneumoniae and Moraxella catarrhalis detection rates were shown in bronchiolitis patients with homozygous A allele than those with other genotypes (20.8% vs. 3.7%, P?<?0.01 and 20.8% vs. 6.2%, P?=?0.03).

Conclusion

The preliminary results demonstrate that IL-17 SNP rs2275913 was associated with several asthma-related traits and confers genetic susceptibility to childhood asthma. It may be used to develop markers to assess the risk of asthma, especially in the bronchiolitis population. It may be a potential bridge to connect the bacterial colonization and the onset of asthma.     

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.     

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.     

Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis

Interleukin-17A plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We investigated the association between ulcerative colitis (UC) and polymorphisms of IL17A, rs2275913 (?197 G > A), and rs3748067 (*1249 C > T). The study was performed in 475 healthy subjects (controls) and 202 with UC (UC cases), including 113 controls and 64 UC cases from previous study. We employed the multiplex PCR-SSCP method to detect gene polymorphisms. The minor allele frequency of rs2275913 was significantly higher but that of rs3748067 was significantly lower in UC cases than controls. The rs2275913 minor homozygote (AA) had an increased risk of the development of UC, whereas rs3748067 minor carrier (CT + TT) had decreased risks for the development of UC. When compared with LR group (rs2275913 GG + GA with rs3748067 CT + TT), HR group (rs2275913 AA with rs3748067 CC) had a more increased risk of the development of UC (OR, 3.38; p = 0.0007). The polymorphisms of IL17A were associated with the noncontinuous and pancolitis phenotypes of UC. Our results suggest that IL17A polymorphisms (both rs2275913 and rs3748067) influence the susceptibility to and pathophysiological features of UC, coordinately.     

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.     

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.     

Association of the suppressor of cytokine signaling 1 (SOCS1) gene polymorphisms with acute coronary syndrome in Mexican patients

Recent studies provide evidence on the emerging role of the SOCS1 gene in the development and progression of atherosclerotic lesions. This gene encodes for the suppressor of the cytokine signaling-1 protein that interacts directly with the Janus kinases that are essential intracellular mediators of the immune cytokine action. The aim of this study was to test for associations between SOCS1 gene single nucleotide polymorphisms (SNPs) and the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. Four SNPs [-3969 C > T (rs243327), -1656 G > A (rs243330), -820 G > T (rs33977706) and +1125 G > C (rs33932899)] of SOCS1 gene were determined for TaqMan genotyping assays in a group of 447 patients with ACS and 622 healthy controls. Under heterozygous model, the -3969 C > T (rs243327) SNP was associated with increased risk of ACS (OR = 1.45, P_Het = 0.021). On the other hand, under co-dominant and heterozygous models, the -1656 G/A (rs243330) SNP was associated with increased risk of ACS (OR = 1.47, P_Co-dom = 0.038 and OR = 1.50, P_Het = 0.013, respectively). Moreover, under co-dominant, dominant, and heterozygous models, the -820 T/G (rs33977706) SNP was associated with increased risk of ACS (OR = 1.59, P_Co-dom = 0.03, OR = 1.48, P_Dom = 0.028 and OR = 1.61, P_Het = 0.01). Finally, under co-dominant and heterozygous models, the +1125 G/C (rs33932899) SNP was associated with increased risk of ACS (OR = 1.54, P_Co-dom = 0.006, OR = 1.58, P_Het = 0.012, respectively). Models were adjusted for gender, age, body index mass, dyslipidemia, alcohol consumption, and smoking. In summary, our data suggests that the four studied polymorphisms of the SOCS1 gene play an important role as susceptibility markers for developing ACS.     

Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages

Four genome-wide RNAi screens have recently identified hundreds of HIV-1 dependency factors (HDFs). Previously, we reported a large variation in the ability of HIV-1 to replicate in monocyte-derived macrophages (MDM) derived from > 400 healthy seronegative blood donors. Here we determined whether SNPs in genes encoding newly identified HDFs were associated with this variation in HIV-1 replication. We found a significant association between the minor allele of SNP rs2304418 in phosphodiesterase 8A (PDE8A) and lower HIV-1 replication (p = 2.4 × 10⁻⁶). The minor allele of SNP rs2304418 was also significantly associated with lower PDE8A mRNA levels in MDM (p = 8.3 × 10⁻⁵). In accordance with this, overexpression of PDE8A in HEK293T cells resulted in increased HIV-1 replication, while subsequent knock-down of PDE8A decreased replication. This study links host genetic variation in a newly identified HDF to variation in HIV-1 replication in a relevant primary target cell for HIV-1 and may provide new leads for treatment of this infection.     

Contribution of syntaxin 1A to the genetic susceptibility to migraine: A case–control association study in the Spanish population

Migraine is a common neurological disorder with a complex inheritance pattern. Mutations in genes encoding proteins that are involved in ion transport across the neuronal membrane have been linked to rare monogenic variants of migraine. These or other related genes and proteins are also candidates to be involved in the inherited predisposition to the more common forms of migraine without aura (MO) or migraine with aura (MA). One of these proteins, syntaxin 1A, encoded by the STX1A gene, is a key molecule in ion channel regulation and synaptic exocytosis. We assessed the contribution of STX1A to migraine by analyzing three SNPs that cover the entire gene (rs6951030–rs941298–rs4363087), in a case–control association study in 210 migraine patients (102 MO, 86 MA, 22 hemiplegic migraine) and 210 sex-matched unrelated controls. The single-marker analysis revealed significant differences in both allele frequencies (P = 0.0087, OR = 1.48) and genotype distributions (P = 0.0133) of the rs941298 SNP between migraineurs and controls, with an overrepresentation of T-allele carriers in the migraine sample (OR = 1.78). We subsequently performed a haplotype-based analysis and observed evidence of an overrepresentation of the A–T–G (rs6951030–rs941298–rs4363087) allelic combination in migraine patients and an increased frequency of carriers of this risk haplotype (P = 0.008, OR = 1.71). These differences remained significant when patients were subdivided into MO and MA. When the control series was enlarged for rs941298, we confirmed the association only with the whole migraine group.     

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.     

Correlation between acute myeloid leukemia and IL-17A,IL-17F,and IL-23R gene polymorphism

Recent studies have shown that Th17 cells may be involved in the pathological process of acute myeloid leukemia. This CD4+ cell subgroup secretes highly homologous interleukin (IL)-17A and IL-17F, and also expresses IL-23 receptor (IL-23R) on the cell surface. Our study aims to investigate the relationship of IL-17A, IL-17F, and IL23R with disease susceptibility, and clarify the relationship between gene polymorphism variation and serum IL-17 level. 62 acute myeloid leukemia patients and 125 healthy controls were included in this study. Restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) was applied to analyze IL-17A (rs2275913; G-197A), IL17F (rs763780; A7488G; His161Arg), and IL-23R (rs11209026, G1142A; Arg381Gln) alleles. At the same time, enzyme-linked immunoassay analysis (ELISA) was used to test serum IL-17 level in patients. Acute myeloid leukemia patients presented higher rate of IL-17F G single mutant (RR = 4.75, P < 0.001) and GG mutation homozygote (RR = 23.01, P < 0.005). While IL-17A, IL-23R A single mutant and purified AA mutation homozygote showed no correlation with acute myeloid leukemia susceptibility. In addition, ELISA showed that serum IL-17 exhibited no significant difference between acute myeloid leukemia patients and healthy controls had (8.8 ± 7.19 pg/ml vs. 1.4 ± 0.2 pg/ml, P > 0.05). IL-17F G single mutant and GG mutation homozygote were correlated with acute myeloid leukemia susceptibility, while IL-17 gene polymorphism and serum IL-17 level were not. Furthermore, IL-17A and IL-23R gene polymorphism were not associated with acute myeloid leukemia susceptibility.