全基因组扫描寻找强直性脊柱炎的易感基因位点

为了寻找中国人群强直性脊柱炎(ankylosing spondylitis,AS)的易感基因位点,采用全基因组扫描法对9个强直性脊柱炎家系进行基因分型、参数连锁分析和非参数连锁分析。在参数连锁分析中,D6S276位点的最大LOD值为3．8821(0=0．0),精细分析显示距D6S276位点附近的D6S1691和D6S1618的LOD值分别为1．5717(0=0．1)及2．0056(0=0．1)。在非参数连锁分析中,位于D6S276附近的LOD值高达5．0623,非参数连锁分析的NPJ值为3．7561,最小P值为0．000233。上述结果提示,D6S276与强直性脊柱炎之间存在较强的连锁关系,D6S1691-D6S276-D6S1618区域可能存在强直性脊柱炎的易感基因位点。此外,D3S1292、D4S1535和D18S64的最大LOD值分别为1．2768(0=0．2)、1．1246(0=0．2)和1．1851(0=0．1),提示这些标记与AS之间存在一定的连锁关系。     

Association Study of Polymorphisms rs4552569 and rs17095830 and the Risk of Ankylosing Spondylitis in a Taiwanese Population

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. However, the development of anklosing spondylitis is unclear. Human leukocyte antigens HLA-B27 and ERAP1 have been widely reported to be associated with AS susceptibility. A recent genome-wide association study (GWAS) showed that two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569) and within ANO6 at 12q12 (rs17095830) contribute to the risk of AS in Han Chinese. In this study, we enrolled 475 AS patients and 475 healthy subjects to assess whether these genetic variations contribute to the susceptibility and the severity of AS in the Taiwanese population. The correlation between genetic polymorphisms, AS activity indexes, (namely, BASDAI, BASFI and BAS-G) and AS complications (uveitis and inflammatory bowel disease) were tested using the markers, rs4552569 and rs17095830. Although no association between rs4552569/rs17095830 genetic polymorphisms and AS susceptibility/severity was found, a significant association between rs17095830 and inflammatory bowel disease was observed in a Taiwanese population.     

IL23R Gene Confers Susceptibility to Ankylosing Spondylitis Concomitant with Uveitis in a Han Chinese Population

Purpose

The interleukin-23 receptor (IL-23R) has been shown to be associated with ankylosing spondylitis (AS) in many different populations. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population.

Methods

Three single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, and rs17375018, were genotyped in 291 AS patients and 312 age-, sex-, and ethnically matched healthy controls using a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assay.

Results

The genotype and allele frequencies of rs17375018, rs7517847, and rs11209032 were not different between the patients with AS and the healthy controls. On the one hand, stratification analysis indicated that the rs17375018 GG genotype and the G allele were increased in AS patients who were HLA-B27 positive (corrected p = 0.024, odds ratio [OR] 2.35, 95% CI 1.30–4.24; p _c = 0.006, OR 1.98, 95% CI 1.28–3.07, respectively). On the other hand, the analysis according to clinical characteristics showed a significantly increased prevalence of the homozygous rs17375018 GG genotype and the G allele in patients with AS and uveitis compared with the controls (p _c = 0.024 and p _c = 0.024, respectively). In addition, haplotype analysis performed with the SHEsis platform revealed no significant difference concerning the haplotypes between AS patients and healthy controls.

Conclusions

In this study, the results suggested that the rs17375018 of IL23R was positively associated with HLA-B27-positive AS and that the rs17375018 GG of IL-23R was associated with AS concomitant with uveitis. We found no evidence for an association between the other two SNPs of IL-23R and AS.     

Analysis of PPARGC1B,RUNX3 and TBKBP1 Polymorphisms in Chinese Han Patients with Ankylosing Spondylitis: A Case-Control Study

Background

Susceptibility to and severity of ankylosing spondylitis (AS) are largely genetically determined. PPARGC1B, RUNX3 and TBKBP1 have recently been found to be associated with AS in patients of western European descent. Our purpose is to examine the influence of PPARGC1B, RUNX3 and TBKBP1 polymorphisms on the susceptibility to and the severity of ankylosing spondylitis in Chinese ethnic majority Han population.

Methods

Blood samples are drawn from 396 AS patients and 404 unrelated healthy controls. All the patients and the controls are Han Chinese and the patients are HLA-B27 positive. The AS patients are classified based on the severity of the disease. Twelve tag single nucleotide polymorphisms (tagSNPs) in PPARGC1B, RUNX3 and TBKBP1 are selected and genotyped. Frequencies of different genotypes and alleles are analyzed among the different severity AS patients and the controls.

Results

After Bonferroni correction, the rs7379457 SNP in PPARGC1B shows significant difference when comparing all AS patients to controls (p = 0.005). This SNP also shows significant difference when comparing normal AS patients to controls (p = 0.002). The rs1395621 SNP in RUNX3 shows significant difference when comparing severe AS patients to controls (p = 0.007). The rs9438876 SNP in RUNX3 shows significant difference when comparing normal AS patients to controls (p = 0.007). The rs8070463 SNP in TBKBP1 shows significant difference in genotype distribution when comparing severe AS patients to controls (p = 0.003).

Conclusions

The rs7379457 SNP in PPARGC1B is related to susceptibility to AS in Chinese Han population. The rs7379457 SNP in PPARGC1B, the rs1395621 and rs9438876 SNPs in RUNX3, and the rs8070463 SNP in TBKBP1 are related to the severity of AS in Chinese Han population.     

rs10865331 Associated with Susceptibility and Disease Severity of Ankylosing Spondylitis in a Taiwanese Population

Ankylosing spondylitis (AS) is a highly familial rheumatic disorder and is considered as a chronic inflammatory disease. Genetic factors are involved in the pathogenesis of AS. To identify genes which render people susceptible to AS in a Taiwanese population, we selected six single-nucleotide polymorphisms (SNPs) from previous genome-wide association studies (GWASs) which were associated with AS in European descendants and Han Chinese. To assess whether the six SNPs contributed to AS susceptibility and severity in Taiwanese population, 475 AS patients fulfilling the modified New York Criteria and 527 healthy subjects were recruited. We found that rs10865331 was significantly associated with AS susceptibility and with Bath AS Function Index (BASFI). The AA and AG genotypes of rs10865331 were also significantly associated with a higher erythrocyte sedimentation rate. Our findings provided evidence that rs10865331 is associated AS susceptibility and with disease activity (BASFI) in a Taiwanese population.     

The Evidence for Association of ATP2B2 Polymorphisms with Autism in Chinese Han Population

Background

Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca²⁺ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population.

Methods

We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses.

Results

This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = −2.482, p = 0.013; Z = −2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180–rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = −2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = −2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values.

Conclusions

Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population.     

Association of AHSG Gene Polymorphisms with Ischemic Stroke in a Han Chinese Population

Previous studies have shown associations of fetuin-A (alpha₂-Heremans-Schmid glycoprotein, AHSG) with various disorders, including insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis. In this study, genotype and allele frequencies of the rs4918 SNP in the AHSG gene were examined in 380 patients with ischemic stroke and 350 healthy controls from a Northern Han Chinese population via the PCR-RFLP technique. Frequencies of the GG genotype and the G allele in AHSG (rs4918) were significantly higher in patients with ischemic stroke or atherosclerotic cerebral infarction than those in the control group (P < 0.05). Logistic regression analysis demonstrated the significance of rs4918 in these patients, after adjustment for confounding factors (P < 0.05). These findings suggest that rs4918 SNPs of the AHSG gene are associated with a risk for ischemic stroke in a Northern Han Chinese population.     

Bone Morphogenetic Protein 6 Polymorphisms Are Associated with Radiographic Progression in Ankylosing Spondylitis

Background and Object

Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.

Methods

A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.

Results

We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74×10⁻⁴) and rs1235192 [OR 1.92, p = 1.17×10⁻³]) adjusted by covariates.

Conclusion

This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.     

Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ² = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ² = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ² = 11.162 and 38.204; p = 0.003 and 4.27×10^-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10^-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ² = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between GRIN2B polymorphisms and SZ susceptibility and symptoms in the Han Chinese population.     

Aberrant Methylation of miR-34b and IL-12B mRNA Promoters Contributes to the Reduced Severity of Ankylosing Spondylitis

DNA methylation of Interleukin-12B (IL-12B) and miR-34b was proved to affect the expression of IL-12B and miR-34b, which were found to be involved in the pathogenesis of ankylosing spondylitis (AS). However, the molecular mechanisms underlying the role of IL-12B and miR-34b in AS remain to be explored. AS patients were divided into four groups according to their status of DNA methylation of miR-34b and IL-12B by bisulfite sequencing: HYPER-miR-34b?+?HYPO-IL-12B, HYPER-miR-34b?+?HYPER-IL-12B, HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups. Functional indicators were examined for patients with different status of DNA methylation in their miR-34b and IL-12B promoters. QPCR was performed to examine the expression of miR-34b and IL-12B mRNA under different conditions. ELISA was used to measure the expression of IL-12B p40 in the peripheral blood. Western blot was used to analyze the expression of IL-12B proteins. Luciferase assay was carried out to explore the suppressive role of miR-34b in IL-12B expression. The level of Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) was gradually increased in HYPER-miR-34b?+?HYPO-IL-12B,HYPER-miR-34b?+?HYPER-IL-12B,HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups, whereas the levels of Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were significantly elevated in the HYPO-miR-34b?+?HYPO-IL-12B group and diminished in the HYPER-miR-34b?+?HYPO-IL-12B group. The expression of miR-34b in the PBMCs and peripheral blood was remarkably higher in the HYPER-miR-34b?+?HYPO-IL-12B and HYPER-miR-34b?+?HYPER-IL-12B groups, whereas the expression of IL-12B was gradually decreased in the HYPER-miR-34b?+?HYPO-IL-12B, HYPER-miR-34b?+?HYPER-IL-12B, HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups. Luciferase assays with the transfection of miR-34b precursors suggested that miR-34b strongly suppressed the expression of IL-12B in THP-1 cells. In conclusion, our study demonstrated that hypermethylated miR-34b promoter led to evident upregulation of miR-34b, thus inhibiting the expression of IL-12B and alleviated the severity of ankylosing spondylitis by reducing the levels of factors including ASDAS-CRP, BASFI and BASMI.

     

Common MIR146A Polymorphisms in Chinese Ankylosing Spondylitis Subjects and Controls

Common polymorphisms of microRNA gene MIR146A were reported as associated with different autoimmune diseases, include systemic lupus erythematosus, psoriatic arthritis, asthma and ankylosing spondylitis. In this study we investigated MIR146A SNPs in Chinese people with ankylosing spondylitis. Three common SNPs: rs2910164, rs2431697 and rs57095329 were selected and genotyped in 611 patients and 617 controls. We found no association between these SNPs and ankylosing spondylitis in our samples.     

Association of OX40L Polymorphisms with Sporadic Breast Cancer in Northeast Chinese Han Population

OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A_rs844648A_rs10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.     

Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population

Background/Aims

Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.

Methodology/Principal Findings

Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23–2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13–1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).

Conclusions/Significance

This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的：研究儿茶酚胺氧位甲基转移酶（COMT）的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法：应用聚合酶链式反应．限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rsl65599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果：上述4个候选基因中,COMT基因rs737865位点C／C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义（P〈0．05）。其余3个位点统计学分析均无显著性差异（P〉0．05）。单倍型分析：上述四个候选基因构建出12种主要单倍型（每种单倍型在对照组和酒依赖组中的频率至少有一个大于1％）,单倍型A—C—A—A有可能是云南汉族酒精依赖发生的一种危险因子（OR：2．865,P=0．003347）。连锁不平衡分析显示：云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁（D〉0．8）。结论：在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C／C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子。云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的:研究儿茶酚胺氧位甲基转移酶(COMT)的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法:应用聚合酶链式反应-限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rs165599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果:上述4个候选基因中,COMT基因rs737865位点C/C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义(P<0.05)其余3个位点统计学分析均无显著性差异(P>0.05)。单倍型分析:上述四个候选基因构建出12种主要单倍型(每种单倍型在对照组和酒依赖组中的频率至少有一个大于1%),单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子(OR:2.865,P=0.003347)连锁不平衡分析显示:云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁(D>0.8)结论:在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C/C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

HLA-DQB1基因多态性与新疆汉族人群结核病易感性的研究

目的:探讨HLA-DQB1基因多态性与新疆汉族人群结核病发生发展的关联.方法:采用PCR-SSP技术对228例新疆塔城地区和石河子地区的肺结核患者及231例健康志愿者的HLA-DQB1的15个等位基因分型,比较各等住基因的频率(GF),并计算其优势比(OR).结果:肺结核病例组DQB1*0201位点的基因频率显著高于对照组(Pc<0.05)其GF和OR分别为10.27%和1.947.结论:HLA-OQB1*0201可能是新疆地区汉族人群结核病发病的易感基因.     

Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ² = 0.15, p = 0.928 by genotype, χ² = 0.14, p = 0.711 by allele; rs763780: χ² = 2.24, p = 0.326 by genotype, χ² = 0.26, p = 0.609 by allele; rs4819554: χ² = 1.79, p = 0.409 by genotype, χ² = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.     

Possible Single-Nucleotide Polymorphism Loci Associated with Systemic Sclerosis Susceptibility: A Genetic Association Study in a Chinese Han Population

Objective

The aim of this study was to confirm the association of RHOB and FAM167A-BLK gene polymorphisms with susceptibility to systemic sclerosis (SSc) in a Chinese Han population.

Methods

A total of 248 SSc patients and 251 healthy controls of Chinese Han ethnicity, which visited the department of dermatology of Peking Union Medical College Hospital, were included in the study. Six selected single nucleotide polymorphisms (SNPs) in the RHOB and FAM167A-BLK regions were selected as markers and were genotyped using a MassARRAY system, which is based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry technique.

Results

Three SNPs in the coding regions of the RHOB and FAM167A-BLK genes displayed an association with SSc: (1) rs1062292T, which is a newly discovered SNP in the RHOB gene (P = 0.03, odds ratio [OR] = 1.62, 95% confidence interval (CI) = 1.05–2.50), (2) rs2736340T (P = 0.03, OR = 1.39, 95%CI = 1.03–1.85), and (3) rs13277113A (P = 0.04, OR = 1.34, 95%CI = 1.01–1.76), both in the FAM167A-BLK gene. Our results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to SSc. However, the loci of the SNPs in RHOB region that displayed an association with SSc are quite different from the loci which were identified in studies of Caucasian populations.

Conclusion

Our results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients. Therefore, variants of the RHOB and FAM167A-BLK genes are promising genetic markers for SSc.     

Genetic Association Study of TNFAIP3, IFIH1, IRF5 Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population

Background

Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.

Methods

A large case–control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform.

Results

Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20–2.16, P_c = 7.5×10⁻³; OR: 1.88, 95%CI: 1.30–2.74, P_c = 4.0×10⁻³, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, P_c = 6.0×10⁻³; OR: 1.88, 95%CI: 1.28–2.76, P_c = 5.5×10⁻³,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P_c = 0.04 and P_c = 0.016; P_c = 0.02 and P_c = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P_c = 0.026 and P_c = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used.

Conclusions

This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.