IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms

Objective: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Method: Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Results: Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2–6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR?=?0.55, 95%CI?=?0.41–0.75; CT versus TT: OR?=?0.54, 95%CI?=?0.40–0.72; CC/CT versus TT: OR?=?0.55, 95%CI?=?0.42–0.72; CC versus CT/TT, OR?=?1.83, 95%CI?=?1.39–2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR?=?0.67, 95%CI?=?0.46–0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR?=?1.77, 95%CI?=?1.39–2.25) and found they were significantly related to the risk of asthma. Conclusion: Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.     

IL-17F gene polymorphism is associated with susceptibility to acute myeloid leukemia

Purpose

Recent studies have suggested that Th17 cells may play a role in the pathogenesis of acute myeloid leukemia (AML). This subset of CD4+ cells is characterized by interleukin (IL)-17A and IL-17F production, which share strong homology, and surface expression of the IL-23 receptor (IL-23R). The present study aimed to determine the association between the polymorphic features located within the IL-17A, IL-17F and IL-23R genes and disease susceptibility, progression and response to therapy. In addition, the relationship between the polymorphic variants and the plasma IL-17 levels in patients was analyzed.

Methods

For this purpose, 187 individuals of Polish origin including 62 AML patients and 125 healthy controls were typed for IL-17A (rs2275913; G-197A), IL-17F (rs763780; A7488G; His161Arg) and IL-23R (rs11209026, G1142A; Arg381Gln) alleles.

Results

The rs763780 IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the minor (G) variant (RR = 4.76, p < 0.001) and its homozygosity (RR = 23.02, p < 0.005) was more frequent among patients than healthy individuals. No significant association was observed for either other polymorphisms studied or IL-17 levels.

Conclusions

Thus, the rs763780 IL-17F polymorphism was found to be associated with predisposition to AML in the Polish population.     

IL-17 Genetic Variations Increase the Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection.

Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome. Objective: This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. Materials and Methods: 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma (C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. Results: Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). Conclusion: Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.     

IL-17A gene polymorphism rs2275913 is associated with the development of asthma after bronchiolitis in infancy

Background

Interleukin-17 (IL-17A) is a mainly pro-inflammatory cytokine, and IL-17 signaling implicates in the development of allergic asthma. The polymorphism rs2275913 in the promoter region of the IL-17A gene has in previous studies been associated with asthma susceptibility. The objective was to evaluate the association between IL-17A rs2275913 (-197G>A) polymorphism and post-bronchiolitis asthma and/or allergic rhinitis in a prospective 11–13 years post-bronchiolitis follow-up.

Evaluation of Th17-related cytokines and IFNγ production from blood mononuclear cells of moderate and severe asthmatic children reveals methylprednisolone does not decrease IL-22 levels

Objective: The aim of this study was to correlate IL-6, IL-17A, IFNγ, and IL-22 production with asthma disease severity and to evaluate if methylprednisolone downregulated cytokine production in peripheral blood mononuclear cells (PBMCs). Methods: Forty-two children with chronic persistent asthma and 34 non-asthmatic children were selected. Cytokines were quantified by ELISA from serum or PBMCs supernatants, after the PMA and Ionomycin stimulation, with or without methylprednisolone at 100?µM. Results: Our data showed undetectable levels of serum cytokines in most patients and controls. In the PBMCs, we have observed a higher production of IL-17A than IL-22 among asthmatics and controls, although it is not statistically significant. IL-6, IFNγ, and IL-17A levels were significantly reduced after methylprednisolone treatment (p?=?0.02, 0.03, and 0.03, respectively) in Severe Persistent Asthma (SPA) and in Moderate Persistent Asthma (MPA), (p?=?0.007, 0.01, and 0.007, respectively). However, IL-22 levels were unaffected (SPA, p?=?0.12 and MPA, p?=?0.93). Conclusion: Methylprednisolone downregulated IL-6, IL17A, and IFNγ, but not IL-22, in stimulated PBMCs from asthmatic children indicating that methylprednisolone has no effect on IL-22 production by PBMCs.     

Sequence variants on 17q21 are associated with the susceptibility of asthma in the population of Lahore,Pakistan

Objective: Single nucleotide polymorphisms (SNPs) on 17q21 are known to be associated with asthma disease in multiple populations. This study was designed to know whether this region is associated with asthma in Lahore region population or not. Methods: A total of 200 asthma patients and 100 healthy controls were enrolled from different hospitals of Lahore, Pakistan. Twelve SNPs from chromosomal region 17q21 were analyzed in cases and controls by single base extension method and capillary-based genetic analyzers. Associations with asthma were checked using basic allelic model, genotypic model, and results were adjusted by logistic regression analysis using PLINK v1.9. Pair-wise linkage disequilibrium among the SNPs was analyzed by using Haploview software. Results: SNP rs3816470 showed a strong association (p?=?8.89?×?10^?5, Odd Ratio?=?3.082 [1.755-5.41]) with asthma, whereas rs3859192 and rs6503525 also showed a significant association with the development of asthma, especially in the case of positive family history. In LD block1 (93?kb) consisting of six SNPs (rs12936231, rs7216389, rs7216558, rs9894164, rs1007654 and rs7212938), none of the haplotypes show any significant association with asthma except the haplotype “CCTCAG”, which is a significant protective factor against asthma having frequency 0.051 in controls while 0.017 in cases (p?=?3.56?×?10^?2, χ²?=?4.415). Conclusion: The present study reports that the polymorphic genomic variant rs3816470 is significantly and independently associated with asthma in the studied population, while the variants, rs6503525 and rs3859192, also indicate a significant association with asthma in this population when family history of the disease is taken as a covariate.     

Serum levels of IL-10, IL-17F and IL-33 in patients with asthma: a case–control study

Objectives: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. Methods: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. Results: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p?p?=?0.001). Conclusions: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments.     

Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability

A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells (p = 0.04) and expression of IL-6 and VCAM1 (p = 0.02, 0.01). Expression of IL-17A and its positive regulators IL-21 and IL-23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients (p = 0.005, 0.004, 0.03), and expression of IL-17A and IL-21 showed a strong correlation (p = 0.002, r = 0.52). The cellular sources of lesional IL-17A expression are T cells, macrophages, B cells and plasma cells. Vulnerable/ruptured (complicated) plaques were significantly associated with IL-17A expression levels (p = 0.003). In addition, IL-17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL-10 (p = 0.0006, r = −0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL-21, IL-23 and VCAM1 (all p < 0.05), but did not influence IL-17A. The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability.     

rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients

Aims: Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia (SCA) by inhibiting deoxy sickle hemoglobin (HbS) polymerization. HbF genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Herein, we aimed to determine whether two functional polymorphisms of BCL11A are implicated in the variation of HbF and clinical events in SCA Tunisian patients.

Material and methods: The studied population consisted of 148 SCA patients with SS phenotype. The group of patients was divided into two subgroups according to the threshold point of %HbF which is 15%. Genotyping of rs11886868 and rs4671393 was performed using PCR/Sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between ‘group who had %HbF?<?15’ and ‘group who had %HbF >15’ (controls) were compared using Pearson's chi-square test (compare 2, version 1.02). The association of each genotype and the combined genotype with complications was performed by logistic regression test.

Results: Our findings showed that the majority of patients carried genotype CT of rs11886868 and genotypes AG and GG of rs4671393 present HbF level?<?15%. RR?=?0.08, RR?=?0.176, and RR?=?0.189, respectively. The results showed a significant association between the alleles T of rs11886868 and G of rs4671393 and %HbF?<?15% with P?=?0.016; RR?=?0.39 and P?=?8.9?×?10^?3: RR?=?0.567, respectively. Interestingly, the C allele of the rs11886868 and the A allele of the rs46713939 were associated with an ameliorated phenotype in patient's SCA. The combination of the genotypes GG and CT explains more phenotypic variance than the sum of the two BCL11A SNPs taken individually.     

Association of IL-13 rs20541 and rs1295686 variants with symptomatic asthma in a Saudi Arabian population

Objective: Interleukin 13 (IL-13) plays a critical pro-inflammatory role in asthma. Several single nucleotide polymorphisms (SNPs) are associated with asthma susceptibility in specific populations; however, further replicative studies in other ethnic groups are mandatory. Methods: The association between IL-13 SNPs rs762534, rs20541, rs1295686, and rs1800925 (risk alleles A, A, T, and A, respectively) and asthma predisposition in a Saudi Arabian cohort was examined via a case–control cross-sectional study. Results: The frequencies of alleles between asthmatics and control populations were significantly different for rs20541 and rs1295686 SNPs (p < 0.001), whereas the frequencies of genotypes between asthmatics and controls were significantly different only for rs20541. The association of the risk (minor) alleles with asthma was examined using the dominant genetic model. Individuals with at least one copy of the risk alleles A (for rs20541) and T (for rs1295686) had significantly greater odds of being asthmatic (OR = 2.13, 95% CI = 1.39–3.26, p < 0.0001; OR = 1.69, 95% CI = 1.12–2.54, p = 0.008) relative to their most common homozygous genotypes. On the other hand, the minor A alleles for rs762534 and rs1800925 were not significantly associated with asthma risk. Regarding haplotype association analysis, individuals with at least one copy of the minor “risk” allele for both rs20541 and rs1295686 (CATG and CATA, respectively) had greater odds of being asthmatic relative to CGCG haplotype; however, this trend was not statistically significant (p > 0.3). Conclusions: IL-13 minor T and A alleles for rs1295686 and rs20541, respectively, were associated with significantly higher risk of asthma in the Saudi Arabian population.     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan

Objective: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. Method: A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T?+?1[rs2280089], T2[rs2280090], T1[rs2280091], ST?+?5[rs597980], ST?+?4[rs44707], S2[rs528557], Q???1[rs612709], and F?+?1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Results: Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p?=?0.0189, Genotype p?=?0.021). SNPs T?+?1[rs2280089], T2[rs2280090], T1[rs2280091], ST?+?4[rs44707], S2[rs528557], and Q???1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype “AAGTCG” in healthy controls suggests a protective effect against asthma risk in the studied population (p?=?0.0059). Conclusion: These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

LRP2 gene variants and their haplotypes strongly influence the risk of developing neural tube defects in the fetus: a family-triad study from South India

Neural tube defects (NTDs) are the leading cause of infant deaths worldwide. Lipoprotein related receptor 2 (LRP2) has been shown to play a crucial role in neural tube development in mouse models. However, the role of LRP2 gene in the development of human NTDs is not yet known. In view of this, family-based triad approach has been followed considering 924 subjects comprising 124 NTD case-parent trios and 184 control-parent trios diagnosed at Institute of Genetics and Hospital for Genetic Diseases, Hyderabad. Blood and tissue samples were genotyped for rs3755166 (?G759A) and rs2544390 (C835T) variants of LRP2 gene for their association with NTDs. Assessment of maternal-paternal genotype incompatibility risk for NTD revealed 3.77-folds risk with a combination of maternal GA and paternal GG genotypes (GAxGG?=?GA,p?<?0.001), while CT genotypes of both the parents showed 4.19-folds risk for NTDs (CTxCT?=?CT,p?=?0.009). Haplotype analysis revealed significant risk of maternal A-T (OR?=?4.48,p?<?0.001) and paternal G-T haplotypes (OR?=?5.22,p?<?0.001) for NTD development. Further, linkage analysis for parent-of-origin effects (POE) also revealed significant transmission of maternal ‘A’ allele (OR?=?2.33,p?=?0.028) and paternal ‘T’ allele (OR?=?6.00,p?=?0.016) to NTDs. Analysis of serum folate and active-B12 levels revealed significant association with LRP2 gene variants in the causation of NTDs. In conclusion, the present family-based triad study provides the first report on association of LRP2 gene variants with human NTDs.

     

白细胞介素-17F A7488G多态性与广东地区胃癌的关系

目的 分析白细胞介素(IL)-17F A7488G(p.His161Arg)多态性与广东地区胃癌遗传易感性及其与胃癌患者临床病理学特征和预后的关系.方法 采用聚合酶链反应-跟制性片段长度多态性(PCR-RFLP)法分析927例胃癌患者及777名健康对照者的IL-17F A7488G多态性,采用Logistic回归法和Cox比例风险法研究其对不同临床病理学特征的胃癌发病风险的影响并进行生存分析.结果 IL-17F A7488G基因型频率在胃癌患者与健康对照人群间差异有统计学意义(X2=16.55,P<0.01).与AA纯合子相比,IL-17F A7488G杂合变异基因型(GA)及纯合变异基因型(GG)显著增加胃癌的发病风险,OR值分别为1.51和1.61(95%CI分别为1.22～1.87和1.03～2.51,P值均<0.01).与AA携带者相比,携带G(GA或GG)等位基因者发生胃癌的风险显著增加(OR=1.53,95%CI:1.25～1.87,P<0.01).按临床病理特征行分层分析显示,IL-17F A7488GGA基因型与肠型、低中分化、非贲门癌、淋巴结转移等的发病风险增加有关.IL-17F A7488G不同基因型患者间生存率差异无统计学意义(P=0.534).结论 广东地区IL-17F A7488G多态性与胃癌易感性有关,IL-17F A7488G变异基因型增加胃癌的发病风险,但不是影响胃癌患者预后的危险因素.     

Increased body mass index predicts severity of asthma symptoms but not objective asthma traits in a large sample of asthmatics

Aim: To examine the relationship between body mass index (BMI) and different indicators of asthma severity in a large community-based sample of Danish adolescents and adults.

Methods: A total of 1186 subjects, 14–44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore height and weight, skin test reactivity, lung function, and airway responsiveness were measured.

Results: A total of 516 individuals had asthma. The mean BMI was 24.9?kg/m² (SD?=?5.1). Asthma severity measured by GINA score increased with increasing BMI (p?=?0.009). The result remained significant after adjusting for age, sex, medication use for asthma and smoking (p?=?0.010). Severity of individual asthma symptoms; cough (p?=?0.002) and chest tightness (p?=?0.023) was also significantly related to BMI, whereas severity of wheezing and shortness of breath was not. Airway obstruction was more pronounced in subjects with increased BMI (p?<?0.001) but the effect disappeared after adjustment for covariates (p?=?0.233). Lung function, airway responsiveness, and atopy were not significantly related to BMI as were use of medication for asthma and adherence to treatment.

Conclusions: In adults, increased body mass index predicts severity of asthma symptoms but not objective asthma traits.     

Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia

Introduction: IL‐17F is a novel inflammatory cytokine and plays an important role in some autoimmune diseases. We investigated the association between chronic ITP and the frequency of the single‐nucleotide polymorphism rs763780 (7488T/C), which causes a His‐to‐Arg substitution at amino acid 161. Patients and methods: We examined 102 patients (men/women, 40/62; median age, 42) diagnosed with chronic ITP and 188 healthy controls (men/women, 78/110; median age, 38). Genotyping was determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) technique. Results: Compared with the control group, patients with chronic ITP had a significantly lower frequency of the IL‐17F 7488CC genotype (0% vs. 4.8%, P < 0.05). The number of IL‐17F 7488C alleles among the patients with chronic ITP was also significantly lower than in the control group (8.7% vs. 15.2% OR = 0.48, 95%CI = 0.27–0.84, P = 0.016). Furthermore, patients with the IL‐17F 7488TT genotype showed a severe thrombocytopenic state (platelet count < 10×10⁹/L) at diagnosis than those with the IL‐17F 7488TC genotype (20.9% vs. 0%, P = 0.04). Conclusion: These findings suggest that the IL‐17F 7488 T allele is significantly associated with the development of chronic ITP, suggesting a role for IL‐17F in the pathogenesis of chronic ITP.     

IL-6, IL-10 and IL-17 Gene Polymorphisms in Iranian Women with Recurrent Miscarriage

Background: Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). Objective: To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women. Method: Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls. Results: The frequencies of IL- 10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls. Conclusion: These results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.     

Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.