Association between interleukin‐21 gene polymorphisms (rs12508721) and HBV‐related hepatocellular carcinoma

Interleukin‐21 (IL‐21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL‐21 gene and susceptibility of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV‐related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction–ligase detection reaction (PCR‐LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL‐21 gene. Our results showed that IL‐21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038–3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV‐related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221–0.920; P = 0.049, OR = 0.482, 95%CI = 0.231–1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV‐related HCC group, chronic HBV‐infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL‐21 gene are associated with the susceptibility of HBV‐related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV‐related HCC. However, the function in these SNPs of IL‐21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV‐related HCC further.     

Genetic association between CD86 polymorphisms and the risk of sepsis in a Chinese Han population

Background

Sepsis is a clinical syndrome that is frequently observed after injury or infection, representing a leading cause of mortality worldwide. CD86 (B7-2) is a co-stimulatory molecule on antigen-presenting cells, and plays critical roles in immune responses.

Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan,Southeast Iran

In this study we aimed to evaluate the possible association of PTPN22 rs2476601 as well as epidermal growth factor receptor (EGFR) rs17337023 gene polymorphism and rheumatoid arthritis (RA) in a sample of Iranian population. This case‐control study was performed on 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood and PTPN22 rs2476601 and EGFR rs17337023 polymorphisms were determined using tetra amplification refractory mutation system–polymerase chain reaction (T‐ARMS‐PCR). The results showed that PTPN22 rs2476601 CT genotype as well as rs2476601 T allele was a risk factor for susceptibility to RA (OR=5.89 95%CI = 1.78–19.48, P = 0.004 and OR = 4.78, 95%CI = 1.59–14.35, P = 0.003, respectively). We also found that EGFR rs17337023 AT and rs17337023 TT genotypes were risk factor for susceptibility to RA (OR = 9.94 95%CI = 3.65–26.73, P < 0.001 and OR = 3.66, 95%CI = 1.46–9.15, P = 0.005, respectively). In addition the EGFR rs17337023 T allele was a risk for predisposition to RA (OR = 1.56, 95%CI=1.06‐2.30, P = 0.030). In conclusion, we found an association between PTPN22 rs2476601 and EGFR rs17337023 polymorphisms and the risk of RA in a sample of Iranian population.     

Polymorphisms in IL‐1A are associated with endometrial cancer susceptibility among Chinese Han population: A case–control study

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL‐1A and several gynaecological diseases. In this research, we analysed the association between IL‐1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL‐1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32–5.92, p = .008; rs3783546: OR = 2.79, 95%CI: 1.32–5.89, p = .008). In the recessive model, we also found that both IL‐1A rs1609682 and IL‐1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32–5.89, p = .0081; rs3783521: OR = 2.80, 95%CI: 1.32–5.92, p = .008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL‐1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations.     

Relationship between polymorphisms in the FAS/FASL death receptor system and progression of low-grade precursor lesions infected with high-risk human papilloma virus

Squamous intraepithelial lesions (SIL) and cervical cancer are primary due to suboptimal immune response against human papillomavirus (HPV). The FASL/FAS system is a trigger of extrinsic pathway apoptosis. The distribution of polymorphisms rs1800682 (−670 A > G) FAS and rs763110 (−844C > T) FASL was studied in cervical smears from 372 females (182 with stable or regressed low-grade SIL (LSIL) (groupI) and a group of 190 high-grade SIL (HSIL) (groupII). No significant differences were observed for rs1800682 in FAS between the study groups. In contrast, rs763110 CC genotype of FASL was found in 35.7% of group I females, and in 50.5% of group II (p = 0.0027; OR = 1.83 (95% CI = 1.21–2.79)). When only females infected with high-risk HPV were analysed, these differences were even higher (p = 0.0024; OR = 2.21 (95% CI = 1.30–3.75)). CC genotype in FASL seems to be associated with increased risk of LSIL to HSIL progression suggesting a role in HPV tolerance, persistent infection, and HSIL development.     

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

The most important anti‐tumour immune response is mediated by T lymphocytes. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) plays a critical role in the immune surveillance against tumours as an inhibitory immune checkpoint molecule of T‐cell activation. This study was designed to explore the association of CTLA4 polymorphisms with the susceptibility to oesophageal squamous cell carcinoma (ESCC) and prognosis of patients with ESCC in a high‐incidence population from northern China. CTLA4 rs5742909 C/T and rs231775 G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction–ligase detection reaction (PCR‐LDR) method in 577 ESCC patients and 580 controls. Upper gastrointestinal cancer family history increased the risk of ESCC (the sex‐, age‐ and smoking status‐adjusted OR = 1.383, 95%CI = 1.094–1.749). The genotype frequencies of these two SNPs in the patients with ESCC were similar to that in the controls. Survival analyses were conducted in 204 patients with ESCC with five‐year survival information. The mean survival time of ESCC patients with rs231775 SNP A/A genotype in age over 60 years group was 23.2 months, significantly shorter than that of those with G/G genotype (47.3 months). The A/A genotype was associated with increased death risk of patients with ESCC older than 60 years (adjusted HR = 4.544, 95%CI = 1.913–10.790). CTLA4 rs231775 SNP might be used as genetic marker of worse prognosis for patients with ESCC over 60 years in a high‐incidence population from northern China.     

TNFSF4 polymorphisms are associated with systemic lupus erythematosus in the Malaysian population

Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T‐cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real‐time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs). Allelic and genotypic frequencies of each SNP were calculated for each ethnic group, and association test was performed using logistic regression. The overall association of each SNP in Malaysian patients with SLE was determined with meta‐analysis. The frequency of minor T allele of TNFSF4 rs2205960 was significant in Chinese and Indian patients with SLE, with P values of 0.05 (OR = 1.27, 95% CI: 1.00–1.61) and 0.004 (OR = 3.16, 95% CI: 1.41–7.05), respectively. Significant association of minor G allele of rs704840 with SLE was also observed in Chinese (P = 0.03, OR = 1.26, 95% CI: 1.02–1.56). However, after Bonferroni correction, only T allele of rs2205960 remained significantly associated with Indian cohort. Overall, minor G allele of rs704840 showed significant association with SLE in the Malaysian population with P values of 0.05 (OR = 1.20, 95% CI: 1.00–1.43). We suggested TNFSF4 rs704840 could be the potential SLE risk factors in the Malaysian population.     

The association of CTLA‐4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population

Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA‐4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA‐4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case–control design. Two single nucleotide polymorphisms (SNPs) in the CTLA‐4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA‐4+49A/G located in exon 1 of the CTLA‐4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17–3.73) using allele‐based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02–8.58). No correlations of at‐risk genotype (G/G) of CTLA‐4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA‐4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.     

Association of HLA-G 3′UTR polymorphisms and haplotypes with colorectal cancer susceptibility and prognosis

Human leukocyte antigen (HLA)-G has been considered as an immune modulator in several types of cancers. Its genetic polymorphisms may potentially affect the risk of developing colorectal cancer (CRC). The overall purpose of this study was to analyze the implication of HLA-G 3′untranslated region (3′UTR) polymorphisms particularly 14 pb insertion/deletion (Ins/Del; rs371194629) and + 3142C/G (rs1063320) in CRC susceptibility and progression.A comparative analysis between patients (N = 233) and controls (N = 241) demonstrated that Del allele (Odds Ratios (OR) = 1.41, 95% CI = 1.091–1.819, p = 0.008), the homozygous Del/Del genotype (OR = 1.80, 95% CI = 1.205–2.664, p = 0.003) and the codominant C/G genotype (OR = 1.59, 95% CI = 1.106–2.272, p = 0.013) were associated to CRC risk. As expected, the DelG haplotype was associated with CRC susceptibility (OR = 1.47, 95% CI = 1.068–2.012, p = 0.018). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele and the homozygous Del/Del genotype were associated with reduced event free survival (EFS) (Respectively, p = 0.009 and p = 0.05). Interestingly, the Del allele and the homozygous Del/Del genotype have been revealed as independent prognostic factors for poor EFS in patients with CRC. Additionally, haplotypes analysis revealed that DelG haplotype was linked with significant increase in CRC risk (log-rank; EFS: p = 0.02). Inversely, the InsC haplotype was associated with a significant reduced CRC risk (log-rank; Overall survival (OS): p < 10^–6; EFS: p = 0.01). Multivariate Cox regression analysis revealed that the InsC haplotype was independently associated with significantly longer EFS (p = 0.021, HR = 0.636, 95% CI = 0.433–0.935).These findings support the implication of HLA-G polymorphisms in the CRC susceptibility suggesting HLA-G as a potent prognostic and predictive indicator for CRC. Insight into mechanisms underlying HLA-G polymorphisms could allow for the development of targeted care for CRC patients according to their genetic profile.     

The level of thymic stromal lymphopoietin and its gene polymorphism are associated with rheumatoid arthritis

ObjectiveTo study the correlation between TSLP gene SNPs and RA in a Han Chinese population.MethodsThe genotypes of TSLP genes rs11466749, rs11466750 and rs10073816 among 197 RA patients and 197 controls were analysed by direct sequencing. ELISA was used to detect the plasma TSLP level. Logistic regression analysis was also conducted to identify risk factors for RA.ResultsThe rs11466749 locus GG genotype (OR = 5.30, 95% CI: 1.76–15.95, P < 0.01), dominant model (OR = 1.68, 95% CI: 1.03–2.73, P = 0.04), recessive model (OR = 5.15, 95% CI: 1.72–15.43, P < 0.01), and G allele (OR = 2.02, 95% CI: 1.33–3.09, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus AA genotype (OR = 4.58, 95% CI: 1.49–14.01, P < 0.01), dominant model (OR = 1.75, 95% CI: 1.09–2.79, P = 0.03), recessive model (OR = 4.27, 95% CI: 1.40–13.00, P = 0.03) and A allele (OR = 1.94, 95% CI: 1.29–2.91, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus GA genotype (OR = 0.29, 95% CI: 0.18–0.45, P < 0.01), dominant model (OR = 0.32, 95% CI: 0.21–0.49, P < 0.01) and A allele (OR = 0.45, 95% CI: 0.32–0.63, P < 0.01) were related to a decreased risk of RA susceptibility. The rs1466749 locus GG genotype, rs11466750 AA genotype, and rs10073816 GG genotype were independent risk factors for RA (P < 0.05). The AUC of plasma TSLP level in the diagnosis of RA was 0.8661 (95% CI: 0.8301–0.9002, P < 0.001). There were statistically significant differences in plasma TSLP levels among subjects with different genotypes at rs11466749, rs11466750, and rs10073816 in the TSLP gene (P < 0.05).ConclusionPlasma TSLP levels are a potential molecular marker of RA. SNPs at rs11466749, rs11466750 and rs10073816 of the TSLP gene are related to the susceptibility of the Han Chinese population to RA.     

Association of IL‐1β +3954 C/T and IL‐10‐1082 G/A Cytokine Gene Polymorphisms with Susceptibility to Tuberculosis

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL‐1β and IL‐10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene–gene interactions. The genotype and allele frequencies of IL‐1β +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059–0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526–5.696) genotypes of IL‐10‐1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1–3.35) genotype in IL‐1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225–9.702) genotype in IL‐10 were at increased risk of developing tuberculosis. MDR tests revealed high‐risk genotypes in IL‐1β and IL‐10 based on the association model. Our results demonstrate that the polymorphisms of IL‐1β and IL‐10 genes may be valuable markers to predict the risk for the development of TB in household contacts.     

The association of CTLA‐4 A49G polymorphism with colorectal cancer risk in a Chinese Han population

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is expressed in T cells and plays an important role in the regulation of T cell. CTLA‐4 has long been considered to be associated with various kinds of diseases. With the attempt to examine the association between CTLA‐4 A49G polymorphism and colorectal cancer risk in a Chinese Han population, we employed TaqMan assay to genotype the CTLA‐4 A49G polymorphism in 311 colorectal cancer cases and 389 cancer‐free controls. We found evidence of the association between CTLA‐4 A49G polymorphism and colorectal cancer risk (GG vs. AA: OR = 2.01, 95% CI = 1.29–3.07, P = 0.002; GA vs. AA: OR = 2.32, 95% CI = 1.53–3.57, P = 0.001; GA + GG vs. AA: OR = 2.16, 95% CI = 1.46–3.21, P = 0.001). Next, we performed a meta‐analysis to comprehensively examine the association between CTLA‐4 A49G polymorphism and colorectal cancer risk. We found a significant association between CTLA‐4 A49G polymorphism and colorectal cancer risk among Asians, which is consistent with our result. However, we found no evidence for the association between CTLA‐4 A49G polymorphism and colorectal cancer risk among Caucasians. In conclusion, we demonstrated that the CTLA‐4 A49G polymorphism increased the susceptibility of colorectal cancer in Asian population.     

Single‐nucleotide polymorphisms of IRF8 gene are associated with systemic lupus erythematosus in Chinese Han population

Interferon regulatory factor 8 (IRF8) has been shown to have diverse roles in the regulation of the immune system. Two recent studies had revealed the association between the single‐nucleotide polymorphisms (SNPs; rs11644034 and rs2280381) of IRF8 and systemic lupus erythematosus (SLE) in a multiethnic population. The purpose of this study was to evaluate whether the association could be replicated in a Chinese Han population. Genotypes were determined by a multiplex polymerase chain reaction–ligase detection reaction (PCR–LDR) in 358 patients and 357 geographically matched healthy controls. Significant differences in genotype frequency were found between SLE and control individuals (rs11644034: AA vs. GG, P = 0.014, odds ratio (OR) = 0.980, 95% confidence internal (CI): 0.964–0.996; rs2280381: CC vs. TT, P = 0.005, OR = 0.150, 95% CI: 0.033–0.676). Conditional logistic regression analysis showed that the association of rs2280381 remained significant (P adjusted = 0.028) after adjustment for rs11644034, but not vice versa (P adjusted = 0.361).When stratifying patients with SLE according to clinical subtypes, SNP rs2280381 was found to be associated with low complement in patients with SLE. However, SNP rs11644034 was not found to be associated with SLE clinical subgroups. Analysis of the haplotypes revealed that haplotype G‐T and G‐C were also significantly associated with SLE (P = 0.002 and P = 0.012, respectively). Our study indicated that the IRF8 gene polymorphisms might be associated with susceptibility to SLE and with disease‐related clinical manifestations in Chinese Han population.     

Association of ABCG2 polymorphisms with ischemic stroke in a Chinese population

ATP‐binding cassette, superfamily G, member 2 (ABCG₂) has been shown to play an important role in the development of ischemic stroke in European and African American populations. The aim of the present study is to test the hypothesis that there are associations between ABCG₂ polymorphisms and ischemic stroke risk in a Chinese population. We conducted a case–control study including 967 participants with ischemic stroke and 939 stroke‐free controls. The rs2231137C > T and rs2231142G > T were genotyped using a TaqMan real‐time polymerase chain reaction assay. We found the rs2231137C > T and rs2231142G > T in ABCG₂ were significantly associated with ischemic stroke (sex‐, age‐, BMI‐, SBP‐, DBP‐adjusted OR = 1.252; 95% CI, 1.035–1.515; P‐value = 0.021 and OR = 1.526; 95% CI, 1.085–2.146; P‐value = 0.015, respectively). By haplotype analyses, the haplotype T‐G still had a strongly significant association with ischemic stroke (OR = 0.806; 95% CI, 0.692–0.939; P‐value = 0.00568). Our findings identified the rs2231137C > T and rs2231142G > T polymorphisms of the ABCG₂ as risk factors for ischemic stroke in a Chinese population.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.     

Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.     

Association of HLA-G,HLA-E and HLA-B*27 with susceptibility and clinical phenotype of enthesitis related arthritis (ERA)

We studied the association of Enthesitis related arthritis (ERA) the most common variant of juvenile idiopathic arthritis (JIA) in Asians, with HLA-G and -E polymorphisms. HLA-G (14 bp Ins/Del rs371194629, +3142 rs1063320, +3187 rs9380142) and HLA-E (rs1264457, and rs2844724) polymorphisms were analyzed in 127 patients with ERA and 381 ethnically matched healthy controls with TaqMan 5′-nuclease assay using allele-specific fluorogenic oligonucleotide probes. HLA-G and -E polymorphisms were not found to be associated with susceptibility to ERA. HLA-G +3187 (rs9380142) G allele was associated with hip arthritis (Pc = 0.04, OR = 2.22, 95%CI = 1.07–4.63) and hip deformity (Pc = 0.02, OR = 2.51, 95%CI = 1.16–5.43). HLA-B*27 was positive in 91. HLA-E rs1264457 G and rs2844724 T alleles may be associated with B*27 positivity in ERA. Among HLA-G, -E haplotypes, frequency of -InsGAAC was significantly higher in patients than healthy controls (Pc = 0.003). In conclusion, HLA-G and HLA-E haplotype -InsGAAC may be associated with susceptibility to ERA and HLA-G +3187 rs9380142 A>G polymorphism may be a poor prognostic marker for progression to hip arthritis and deformity in ERA-JIA.     

Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR‐RFLP technique was used to detect IL10 promoter genotypes at the positions of ?1082 (G/A), ?819 (C/T) and ?592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of ?1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21–5.82), p‐value = 0.046]. The CC genotype in ?819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26–9.07), p‐value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15–3.01), p‐value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of ?592 SNP and decreased in AA genotype carriers of ?1082. IL10 was also increased in SLE patients with CGT (?592/?1082/?819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of ?592 and TT genotype carriers at the region of ?819. SLEDAI was also elevated among patients with CGC (?592/?1082/?819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 –819(C/T), ?1082(G/A) and ?592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings.     

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women

ObjectiveThe aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.Study designWe genotyped the INHA polymorphisms c.-16C > T (rs35118453) and c.-124A > G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.ResultsThere were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T–G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR = 1.630, 95% CI = 1.081–2.457). Combination genotype analysis showed that the CT + TT/GG genotype frequency was higher in POI patients than in the controls (OR = 2.414, 95% CI = 1.190–4.895).ConclusionsWe provide evidence to suggest that when the two variant alleles are combined, the c.-16C > T and c.-124A > G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.