Association between IL-33 Gene Polymorphisms (rs1929992, rs7044343) and Systemic Lupus Erythematosus in a Chinese Han Population

Objective: Interleukin-33 (IL-33) is a member of the IL-1 family, and previous studies found the single-nucleotide polymorphisms (SNPs) in the IL-33 gene was related to susceptibility to autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis and Behcet’s disease. To date, no study has discussed the potential association between IL-33 gene polymorphisms and systemic lupus erythematosus (SLE).

Methods: We conducted a case-control study including 371 SLE patients and 408 healthy controls to investigate the correlation between the SNPs of IL-33 gene (rs1929992, rs7044343) and SLE in a Chinese Han population.

Results: There was significantly lower expression of allele G for rs1929992 in SLE patients than that in controls (G versus A, P = 0.012, OR = 1.310, 95% CI: 1.060–1.624 after adjustment with sex). Similarly, genotype GG was associated with the susceptibility to SLE as compared with the AA genotype (P = 0.017, OR = 1.714, 95% CI: 1.101–2.669 after adjustment with sex). We also found statistical significance in the dominant model (GG+GA versus AA, P = 0.017, OR = 1.481, 95% CI: 1.074–2.044 after adjustment with sex). However, we found no strong evidence for the association of IL-33 rs7044343 polymorphism with SLE. Moreover, association studies were performed on the relationship between the IL-33 gene polymorphisms and lupus nephritis as well as nine clinical features of SLE, but there was no significant association regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of sub-phenotypes.

Conclusion: Our findings indicate that IL-33 rs1929992 polymorphism may be a potential biomarker for susceptibility to SLE.     

Association Study of ARL15 and CDH13 with T2DM in a Han Chinese Population

Several studies indicate that plasma adiponectin levels are associated with the risk of type 2 diabetes mellitus (T2DM) or T2DM risk factors in diverse populations. In addition to the adiponectin gene, several other genes have been postulated to influence plasma adiponectin levels. In this study, we investigated two single nucleotide polymorphisms (SNPs), rs4311394 and rs4783244, located intronically in the ADP-ribosylation factor-like protein 15 (ARL15) and the T-cadherin (CDH13) genes, respectively. These SNPs were detected in a Han Chinese population using a TaqMan assay and evaluated for association with T2DM as well as with individual metabolic traits. Allele frequencies for rs4311394 were significantly different in T2DM and nondiabetes (NDM) groups (χ² = 4.49, P = 0.034). However, neither allele nor genotype frequencies for rs4783244 were associated with T2DM (χ² = 0.33, P = 0.56 and χ² = 2.35, P = 0.31 respectively). The SNPs did not exhibit significant association with individual metabolic traits in the T2DM and NDM groups. Our results indicated that the G allele of the rs4311394 might be a susceptibility factor for T2DM in the Han Chinese population (odds ratio: 1.20; 95% confidence interval: 1.01-1.41).     

Association study of SCARB2 rs6812193 polymorphism with Parkinson's disease in Han Chinese

Recently, a nucleotide polymorphism rs6812193 near SCARB2 was found to be significantly associated with Parkinson's disease (PD) in populations of European ancestry. Herein, we conducted a case-control study with attempt to further evaluate the association between SNP rs6812193 and PD in a Chinese population from mainland China. rs6812193 was genotyped by PCR-RFLP technique in 449 PD patients and 452 controls in a Chinese population. In our study, we did not detect statistically significant differences between cases and controls in terms of both allele and genotype distribution of the rs6812193 polymorphism (P=0.97 and P=0.77, respectively), even after stratification by age at onset. Our data do not support the association of SNP rs6812193 with PD in Han Chinese of mainland China.     

Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia

Background

The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT₃ receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT₃ receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity.

Methods

Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia.

Results

HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90).

Conclusions

The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT₃ mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

     

G Protein β3 Subunit Gene Variants and Essential Hypertension in the Northern Chinese Han Population

Recently a novel C825T polymorphism in the G protein β3 subunit gene was identified that showed an association with hypertension in a German population; the results of studies in other populations have been inconsistent. To examine the contribution of GNB3 polymorphisms to the development of hypertension in the northern Chinese Han population, we conducted a case‐control study consisting of 501 hypertensive cases and 503 controls using the G(‐350)A, C825T and C1429T polymorphisms. Genotypes of samples were determined by PCR and restriction digestion. Single locus analysis showed a significant association between G(‐350)A and hypertension (P = 0.01) but no association for C825T or C1429T. The three polymorphisms were in tight linkage disequilibrium (D′=?1 for G(‐350)A‐C825T, D′= 0.92 for C825T‐C1429T) and a total of 7 haplotypes were observed in the entire population. Haplotype A‐C‐C was found to be significantly related to hypertension (P = 0.032) and A‐C‐C carriers had a more than two‐fold higher risk of hypertension than non‐carriers, after adjustment for BMI and glucose. In conclusion, our study suggests that G(‐350)A is a potential functional polymorphism that may be related to hypertension, whereas the C825T and C1429T polymorphisms are not associated with hypertension in the northern Chinese Han population.     

Analysis of Functional SNP in Ifng/Ifngr1 in Chinese Han Population with Tuberculosis

Ifng/Ifngr1 are the main genes that are associated with tuberculosis. We continued to search for other functional single nucleotide polymorphisms (SNP) and investigated their influence on patients with tuberculosis in the Chinese population. Seven SNP located in the ifng and ifngr1 genes were genotyped by ligase detection reaction in 222 cases and 188 ethnically matched controls. A significant genetic association between rs7749390 (located on the exon/intron splice site of the ifngr1 gene) and tuberculosis was observed, and the log‐additive model was accepted as the best inheritance model to fit these data (OR: 1.35, 95% CI: 1.02–1.80, P = 0.038). Haplotype‐specific association analysis revealed that the result was consistent with the individual SNP study. The combination of rs2234711/rs1327474/rs7749390/rs41401746, which was in strong linkage disequilibrium (D′ > 0.75), showed a significant association of ifngr1 with tuberculosis (P = 0.00079). Neither the single SNP nor the haplotype analysis showed a significant association between tuberculosis and the ifng gene markers. Our data implied the involvement of the ifngr1 gene in susceptibility to tuberculosis.     

OX40基因rs2298212位点与汉族人群冠状动脉粥样硬化疾病的关联研究

Objective To study the association of the OX40 gene rs2298212G/A polymorphism with coronary atherosclerotic disease (CAD) in Chinese Han population. Methods Five hundred and thirty six CAD patients and 544 age and ethnic matched controls of Chinese Hah population were recruited from Qilu Hospital, Shandong University. Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was used to genotype the selected single nucleotide polymorphism. Distributions of genotypic and allelic frequencies were analyzed by Chi square test. Results The distribution of genotypic and allelic frequencies have no significant differences between the CAD cases and controls (P＞0.05), even after adjusting for age, gender, body mass index, systolic blood pressure, diastolic blood pressure, glucose, total cholesterol, and triglyceride. However, when substratification analysis of the involved coronary artery vessels was performed, significant difference was found between single-vessel and triple-vessel (P=0.02,OR=1.56,95%CI:1.08-2.26) involvement. Conclusion The rs2298212G/A polymorphism in OX40 gene may be associated with the severity of coronary atherosclerotic disease.     

OX40基因rs2298212位点与汉族人群冠状动脉粥样硬化疾病的关联研究

目的 探讨OX40基因(TNFRSF4)rs2298212G/A位点与山东汉族人群冠状动脉粥样硬化疾病的相关性.方法 在山东大学齐鲁医院心内科和健康体检中心分别收集到冠状动脉粥样硬化疾病患者536例和正常对照544名,采用聚合酶链反应-限制性片段长度多态性方法 对OX40基因rs2298212G/A多态性位点进行基因分型,并对数据进行统计分析.结果 基因型与等位基因频率分布在病例组与对照组之间差异均无统计学意义(P＞0.05).在回归校正了年龄、性别、体重指数、收缩压、舒张压、血糖、总胆固醇及甘油三酯等因素的影响后,基因型频率分布差异仍无统计学意义(P＞0.05).在对冠状动脉受累支数进行的分层分析发现,受累1支与受累3支之间,基因型与等位基因频率分布差异均有统计学意义(P＜0.05).结论 OX40基因rs2298212G/A多态位点同山东汉族人群冠状动脉粥样硬化疾病之间无关联性存在,但该位点可能与冠状动脉粥样硬化的严重程度相关.     

OX40基因rs2298212位点与汉族人群冠状动脉粥样硬化疾病的关联研究

Objective To study the association of the OX40 gene rs2298212G/A polymorphism with coronary atherosclerotic disease (CAD) in Chinese Han population. Methods Five hundred and thirty six CAD patients and 544 age and ethnic matched controls of Chinese Hah population were recruited from Qilu Hospital, Shandong University. Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was used to genotype the selected single nucleotide polymorphism. Distributions of genotypic and allelic frequencies were analyzed by Chi square test. Results The distribution of genotypic and allelic frequencies have no significant differences between the CAD cases and controls (P＞0.05), even after adjusting for age, gender, body mass index, systolic blood pressure, diastolic blood pressure, glucose, total cholesterol, and triglyceride. However, when substratification analysis of the involved coronary artery vessels was performed, significant difference was found between single-vessel and triple-vessel (P=0.02,OR=1.56,95%CI:1.08-2.26) involvement. Conclusion The rs2298212G/A polymorphism in OX40 gene may be associated with the severity of coronary atherosclerotic disease.     

Emerging Role of SIGIRR rs7396562(T/G) Polymorphism in Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with heterogeneous presentation. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs7396562, of the interferon induced with single immunoglobulin IL-1-related receptor (SIGIRR) gene with SLE in a Chinese population. A total of 741 SLE patients and 731 healthy control subjects were enrolled in the present study. The genotyping of polymorphism (rs7396562) was determined by TaqMan allele discrimination assay on the 7,300 real-time polymerase chain reaction system. The frequency of T allele for rs7396562 in patients was significantly higher than in controls (T versus G, OR?=?1.318, 95 % confidence interval (CI)?=?1.139–1.525, P?P?versus GG, P?=?0.002; TT versus TG?+?GG, P?=?0.002). We also analyzed the association of the SIGIRR rs7396562 T allele with clinical features; luckily, photosensitivity and malar rash had some significant signal with the SNP. In conclusion, our study represents the first report demonstrating an association of the SIGIRR rs7396562 polymorphism with SLE susceptibility in a Chinese population.     

Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 (IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio?=?1.20, 95 % confidence interval?=?1.02–1.40). However, no significant difference in genotype distribution was found between cases and controls (P?=?0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P?=?0.06; TT versus TC + CC, P?=?0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population.     

Association of Inducible T Cell Costimulator Polymorphisms with Susceptibility and Outcome of Hepatitis B Virus Infection in a Chinese Han Population

Inducible T cell costimulator (ICOS) functions to regulate cell–cell signalling, immune responses and cell proliferation. ICOS single nucleotide polymorphism (SNP) may affect protein expression and functions. This study investigated the association of ICOS SNPs with hepatitis B virus (HBV) infection and outcome in a Chinese population. A total of 1290 Chinese Han individuals were enrolled, including 63 asymptomatic HBV carriers, 220 chronic hepatitis B patients (CHB), 249 HBV‐related liver cirrhosis patients (LC), 108 patients with HBV‐related hepatocellular carcinoma (HCC), 338 patients with natural HBV clearance and 312 healthy subjects (as controls). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931 and rs4675379) using TaqMan SNP Genotyping Assay and analysed. The data showed that genotype and allele frequencies of ICOS SNPs in cases and controls followed the Hardy–Weinberg distribution. The CC genotype of rs4675379 was higher in patients with HBV infection (including AC, CHB, LC and HCC) than in patients with HBV clearance (P = 0.006). Furthermore, the genotype ‘GA’ and the minor allele ‘A’ of rs1559931 were associated with a decreased HCC susceptibility (P < 0.001). Haplotype analysis data showed that ‘GC’ haplotype in block 2 (rs1559931 and rs4675379) had a lower frequency in patients than in HBV‐cleared subjects (P = 0.034), although its overall frequency was only 1.6%. Our study found that ICOS rs1559931 SNP was associated with decreased HBV‐related HCC risk in the studied Chinese Han population, except for patients with natural clearance of HBV.     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

糖皮质激素受体遗传多态性与2型糖尿病相关性研究

目的 探讨糖皮质激素受体(GR)单核苷酸多态性与2型糖尿病(T2MD)易感性及人体体型的相关性.方法 采用病例-对照研究设计,从解放军总医院健康体检中心的体检患者中,募集40例T2MD患者和127例对照.结合三种不同的SNP位点选择方法,采用上海天昊生物科技有限公司的iMLDRTM多重SNP分型技术对入选SNP位点进行基因分型.采用非条件Logistic回归,校正年龄、性别、吸烟、饮酒后,分析基因型与T2MD易感性的关系.得到的阳性位点,进一步采用协方差分析,校正年龄、性别、吸烟、饮酒后,评价其与体重指数(BMI)和腰臀比(WHR)的相关性.结果 共选取14个SNP位点,其中rs10052957突变型在病例组中频率为零,故未纳入统计分析.所有的13个SNP位点在病例和对照组中的基因分型均符合Hardy-Weinberg平衡.rs9324924 TT基因型(OR [95％CI]=3.12[1.06 ～9.17],P=0.039)和rs9324921 AA基因型(OR [95％CI]=14.92[1.39～160.60],P=0.026)发生T2DM的风险较野生型增高,且两基因型的BMI[P=0.023 (rs9324924);P=0.002(rs9324921)]、WHR[P=0.033 (rs9324924);P=0.003(rs9324921)]也较野生型明显增高.结论 在本研究中,GR基因rs9324924、rs9324921与T2DM易感性和体型有关,其中纯和突变型T2DM发病风险明显增加,且更具有肥胖倾向.     

Association of HLA-DQA1 (rs9272219) with susceptibility to rheumatoid arthritis in a Han Chinese population

HLA-DQA1 (rs9272219) has been previously reported that it is a susceptibility locus in rheumatoid arthritis (RA) of UK Caucasian population and North American; however, it has not reported in RA of Chinese population. Our study was to identify whether or not this relationship is reside between rs9272219 and RA in a Han Chinese population. 207 patients with RA and 199 control subjects were recruited. The single nucleotide polymorphism (SNP) of rs9272219 was tested in alleles and genotype frequencies and the data was analyzed by doing the statistic analysis of odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses after pairwise linkage disequilibrium (LD) was estimated. Finally, the Alleles and genotype frequencies distribution of rs9272219 locus among RA patients and control subjects were in accordance with Hardy-Weinberg equilibrium. We found significant association between rs9272219 and RA of Chinese population (OR 0.494, 95% confidence interval [95% CI] 0.354-0.688, P = 0 and OR 2.541, 95% CI 1.695-3.808, P = 0, respectively). In this study, we found that the SNP of rs9272219 in HLA-DQA1 is a potential susceptibility locus in RA of Han Chinese population; the results suggest that HLA-DQA1 may be related to the development of RA.     

Positive Association between GCKR rs780093 Polymorphism and Coronary Heart Disease in the Aged Han Chinese

Objective. Previous studies have confirmed that GCKR rs780093 polymorphism is associated with triglyceride (TG), a known risk factor of coronary heart disease (CHD). The goal of our study is to explore the association of GCKR rs780093 polymorphism with CHD in Han Chinese population. Methods and Results. A total of 568 CHD cases and 494 non-CHD controls were enrolled in the current case-control study. Genotyping was done using melting temperature shift (Tm-shift) approach. Our results also showed that GCKR rs780093 polymorphism was significantly associated with TG level (P = 0.0016). Although there was no significant association between cases and controls (P > 0.05), a breakdown analysis by age yielded a significant association of GCKR rs780093 polymorphism with CHD in individuals aged 65 and older (genotype: χ² = 6.86; df = 2; P = 0.03; allele: χ² = 4.11; df = 1; P = 0.04). Conclusion. Our findings confirmed the contribution of GCKR rs780093 polymorphism to TG metabolism and demonstrated GCKR rs780093 as a risk factor of CHD in individuals aged 65 and older.     

BARD1单核苷酸多态性与汉族儿童神经母细胞瘤相关性的研究

目的 探讨BARD1单核苷酸多态性与汉族儿童神经母细胞瘤的相关性.方法 采用病例对照研究,收集242例汉族神经母细胞瘤患儿及301例汉族健康儿童的外周血,通过PCR方法扩增目的DNA,应用Sequenom massarray对所扩增的DNA进行基因分型.以x2检验及logistics分析比较不同组基因型与神经母细胞瘤的关系.结果 BARD1的21个标签SNPs位点均符合Hardy-Weinberg平衡,BARD1的21个SNPs等位基因频率在患者组与对照组之间差异均无统计学意义(P＞0.05).结论 未发现BARD1单核苷酸多态性与汉族儿童神经母细胞瘤有相关性.     

CD11b单核苷酸多态性与中国汉族系统性红斑狼疮的研究

目的 分析CD11b基因rs1143679的单核苷酸多态性(SNP)在中国汉族系统性红斑狼疮(SLE)患者中的表达,并阐明该SNP与SLE临床表型的相关性.方法 采用病例对照的研究方法,应用PCR-PFLP以及直接测序技术对中国汉族人群中584例系统性红斑狼疮患者和624例健康对照者进行多态性检测,分析基因型和等位基因频率的分布差异,并与临床表型进行相关性分析.结果 (1)SLE患者中CD11b rs1143679 GA基因型频率为1.89％,大大低于欧美国家的基因型频率,与香港及泰国地区接近.(2) CD11b rs1143679 GA基因型与狼疮肾炎有相关性(P=0.01),而与发病时间、关节炎、血液系统、神经系统损害没有统计学差异(P＞0.05).结论 CD11b rs1143679 SNP与中国汉族人群系统性红斑狼疮易感性有关,并可能参与了狼疮肾炎的发生发展.