STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians

The aim of this study was to determine the influence of STAT4 (rs7574865) and TRAF1/C5 (rs10818488 and rs2900180) gene polymorphisms on the risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Colombian population. This was a case-control study in which 839 individuals with RA (N=274) and SLE (N=144) and matched healthy controls (N=421) were included. Genotyping was performed by using a polymerase chain reaction system with pre-developed TaqMan allelic discrimination assay. STAT4 rs7574865T allele disclosed a significant influence on the risk of developing SLE (P=0.0005; OR 1.62, 95% CI 1.22-2.16) and RA (P=0.008; OR 1.36; 95% CI 1.08-1.71), whereas no effect on these autoimmune diseases was observed for the TRAF1/C5 polymorphisms examined. Our data strengthen STAT4 rs7574865 polymorphism as a susceptibility factor for RA and SLE and provide further evidence for a common origin of autoimmune diseases.     

Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China

ABSTRACT: BACKGROUND: To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China. METHODS: Blood samples were collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems(R) TaqMan(R) SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064). RESULTS: One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC [OR (95 % CI) =1.53 (1.02-2.29)], and genotypes rs4147064 CT [OR (95 % CI) =1.872 (1.082-3.241)], and rs9551963 AC [OR (95 % CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG [OR (95 % CI) = 2.926 (1.18-7.251)] increased the risk of, while rs4073259 GG [OR (95 % CI) = 0.381 (0.157-0.922)] decreased the risk of cerebral infarction in patients with diabetes. CONCLUSION: These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.     

No evidence of association of the KLF12 gene with rheumatoid arthritis in Spanish and Dutch cohorts and a meta-analysis of published data

The aim of the present study was to replicate the previously reported association of KLF12 gene polymorphisms with rheumatoid arthritis (RA). Two independent cohorts from Spain (1,360 RA patients and 1,520 controls) and the Netherlands (1,018 RA patients and 1,150 controls) were genotyped for KLF12 rs1887346 and rs9565072 single-nucleotide polymorphisms using a TaqMan 5'-allele discrimination assay. No evidence of association of RA with the minor T allele of rs9565072 (31.82% vs 33.73%; p = 0.14, odds ratios [OR] 0.92 [95% confidence interval (CI) 0.82-1.03]) or the minor A allele of rs1887346 polymorphism (21.60% vs 21.77%; p = 0.88, OR 0.99 [95% CI 0.87-1.13]) was observed in Spanish patients compared with healthy controls. This lack of association was also confirmed in the Dutch cohort: the minor T allele frequency of rs9565072 in Dutch RA patients was 35.34% versus 35.57% in controls; p = 0.87, OR 0.99 (95% CI 0.87-1.12); and the minor A allele frequency of rs1887346 in Dutch RA patients was 27.64% versus 28.17% in controls; p = 0.70, OR 0.97 (95% CI 0.85-1.12). A meta-analysis of published KLF12 gene association with RA revealed a pooled OR of 0.99 (95% CI 0.93-1.04) for rs1887346 and a pooled OR of 0.99 (95% CI 0.95-1.04) for rs9565072. In conclusion, our findings indicate that the KLF12 rs1887346 and rs9565072 polymorphisms do not play a relevant role in RA.     

骨保护素基因单核苷酸多态性与类风湿关节炎发病的相关性研究

 目的：探讨骨保护素（OPG）基因163A/G及245T/G单核苷酸多态性（SNPs）与我国汉族人群类风湿关节炎（RA）发病的相关性。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测我国南方汉族正常人群及RA患者的OPG 163A/G 和245T/G 2个SNP位点;进行Hardy-Weinberg平衡检验;计算基因型和等位基因频率,及这2个位点的连锁关系,并分析这2个SNP位点与RA的关系。结果：所研究基因分布符合Hardy-Weinberg平衡,163A/G 位点基因型AA、AG、GG分布频率在2组比较有显著差异（P<0.05）;等位基因A、G分布比较在2组有显著差异（P<0.05）,携带163GG基因型者发生RA的危险性是非携带者的1.219倍（OR=1219, 95％CI：1066~2.339, P<0.05)。但245T/G位点各基因型及等位基因频率在2组中均未见差异（P>005）。结论：OPG 基因 163A/G SNP可能与我国汉族人群RA发病相关,携带G等位基因可能是发病的危险因素。     

TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels

Alzheimer disease (AD), vascular dementia, and stroke are all associated with inflammation though their respective initiating factors differ. Recently a polymorphism in the proinflammatory cytokine tumor necrosis factor (TNF), in association with apolipoprotein E (APOE), was reported to increase AD risk. Two SNPs, rs1799724 (-850C>T; NT_007592.14:g.22400733C>T) and rs1800629 (-308G>A; [NT_007592.14:g.22401282G>A]), and the APOE polymorphism were genotyped in 506 patients with sporadic AD and in 277 cognitively healthy controls. In a subset of 90 individuals we also investigated whether these SNPs exerted any functional effects on cerebrospinal fluid (CSF) beta-amyloid (Abeta) levels. The frequency of the rs1799724 genotypes and the rs1799724-T allele were significantly different in AD individuals (P=0.009; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.13-2.34), while the rs1800629 SNP was not associated with AD. Significant interaction was observed between the rs1799724-T and APOE epsilon4 alleles in that the rs1799724-T allele significantly modified risk associated with possession of the epsilon4 allele only (epsilon4 in absence of rs1799724-T: OR, 2.92; 95% CI, 2.00-4.27; epsilon4 in presence of rs1799724-T: OR, 6.65; 95% CI, 3.26-13.55; P=0.03). Haplotyping analysis revealed a significant overrepresentation of an rs1799724-T/rs1800629-G haplotype in AD (P=0.012; OR, 1.60; 95% CI, 1.11-2.29), although to a lesser degree than rs1799724-T alone. Further, the rs1799724-T allele was found to be associated with lower levels of CSF Abeta42 (P=0.023), thus corroborating the genetic findings. Inheritance of the rs1799724-T allele appears to synergistically increase the risk of AD in APOEepsilon4 carriers and is associated with altered CSF Abeta42 levels. Further investigations are warranted to assess the significance of these novel findings.     

Inhibitors of kB-like gene polymorphisms in rheumatoid arthritis

OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G, and -62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421 was significantly different between DR4(+) RA patients and DR4(+) controls (p = 0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+) RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4-147.0). We also found that the allele frequency of IkBL -62 T was significantly higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1). The allele carriage frequency of IkBL -62 T tended to be increased in RA patients (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL -421 8T/-62 T tended to be increased in RA patients compared with controls (p = 0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated with the development of RA in Taiwan. The IkBL -421 8T may also be related to susceptibility to RA in HLA-DR4(+) individuals. This study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to RA in Taiwan.     

Association of PTPN22 single nucleotide polymorphism with rheumatoid arthritis but not with allergic asthma

PTPN22 gene encodes a lymphoid tyrosine phosphatase (LYP), an important negative regulator of T-cell responses. The 1858C>T (Arg620Trp) single nucleotide polymorphism (rs2476601) was found associated with autoimmune diseases, including rheumatoid arthritis (RA). Allergic diseases are similar to autoimmune diseases, by an exaggerated immune response to an antigen (allergen in this case) normally not invoking such response in healthy individuals. We investigated whether polymorphism 1858C>T in PTPN22 gene is associated with susceptibility to allergic asthma and RA in a Polish population. PTPN22 was genotyped in 173 patients with RA, in 198 patients with allergic asthma, and in 543 controls using PCR-RFLP. The patients with RA differed from healthy controls in frequencies of PTPN22 1858C>T alleles (P=0.0004; odds ratio (OR), 1.8; 95% CI, 1.33-2.55) and genotypes (P=0.0009). Strong associations of 1858T allele with RA limited to joints (0.21 vs 0.12, P=0.0002; OR, 2.1; 95% CI, 1.44-3.00), with erosive disease (0.20 vs 0.12, P=0.0003; OR, 1.92; 95% CI, 1.34-2.71), with a lack of rheumatoid factor (RF; 0.23 vs 0.12, P=0.0008; OR, 2.29; 95% CI, 1.44-3.63), and weak association with the presence of RF (0.17 vs 0.12, P=0.02; OR, 1.6; 95% CI, 1.10-2.40) in comparison with healthy controls were observed. Very strong association of 1858T allele (P<0.0001; OR, 2.72; 95% CI, 1.9-3.9) and T phenotype (P<0001; OR, 3.2; 95% CI, 2.1-4.9) with antibodies to cyclic citrullinated peptide (CCP) was found. When patients with allergic asthma were typed for PTPN22 1858C>T polymorphism, no difference with control was found. Subdivision of patients into those with mild, moderate, or severe asthma did not reveal any associations. In conclusion, we confirmed associations between several clinical manifestations of RA and PTPN22 1858T allele. However, no association with 1858C>T polymorphism was found for susceptibility to allergic asthma or for severity of the disease.     

Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid arthritis

Human allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein primarily identified in human and rat allografts, and data from several studies suggest an important role for AIF-1 in inflammatory processes. The aim of this study was to examine the association between AIF1 rs2269475:C>T polymorphism and rheumatoid arthritis (RA). AIF1 genotype was determined by means of the polymerase chain reaction-restriction fragment length polymorphism method in 276 White patients with RA and 236 healthy subjects. The frequency of the AIF1 rs2269475 TT genotype was significantly higher in the patients with RA than in the controls (OR=5.59, 95% CI: 1.22-25.55). The frequency of T allele carriers in the patient group with RA was 31.9% vs 19.1% among controls (P=0.0003). Moreover, the frequency of individuals positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies was significantly elevated in the T allele carriers (OR=8.82, 95% CI: 2.06-37.7). It is noteworthy that no significant linkage disequilibria between the AIF1 C/T and DRB1 alleles associated with RA development and anti-CCP antibody production [including the most frequent, i.e. *04 (32.7%) and *01 (23.5%)] (P>0.1) were found. Our results show that the AIF1 rs2269475 T allele is associated with increased risk of RA development. Moreover, the frequency of individuals positive for anti-CCP antibodies is significantly increased among T allele carriers.     

Polymorphic variants of the IL2RA gene and susceptibility to type 1 diabetes in the Polish population

Polymorphic variants of the IL2RA gene, which encodes high-affinity alpha subunit (CD25) of the interleukin-2 receptor, were recently found to affect the risk of several autoimmune disorders. This study was aimed to investigate the association of selected IL2RA polymorphisms (rs11594656, rs3118470, rs2104286 and rs7093069) with type 1 diabetes (T1D) in a Polish cohort comprising 445 patients and 671 healthy control subjects. The minor A allele at rs11594656 was found significantly less frequently among T1D subjects, compared with the control group [P = 0.011; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.629-0.942]. In contrast, the minor C allele at rs3118470 appeared to be significantly associated with the occurrence of T1D (P = 0.003; OR = 1.30; 95% CI = 1.094-1.550). Two other IL2RA single nucleotide polymorphisms (SNPs) did not show significant differences among investigated groups. In conclusion, the study confirms the association of the IL2RA locus with T1D in the Polish population.     

IL-33基因单核苷酸多态性与中国南方汉人炎症性肠病临床表型相关*

 目的：探讨白细胞介素33（IL-33）基因单核苷酸多态性（SNP）与中国南方汉人炎症性肠病（IBD）的关系。方法：通过HapMap数据库筛选出IL-33基因8个SNP序列标签;对250例克罗恩病（CD）患者、115例溃疡性结肠炎（UC）患者及622名健康对照采用MALDI-TOF MS技术进行基因分型检测。结果：8个SNP位点的基因型及等位基因频率在病例（包括CD及UC）及对照组中无明显差异（P>0.05）。基因型-临床表型分析发现多个SNP位点与CD部分临床表型相关：rs10118795 T等位基因是肠外表现的保护因素（P<0.05, OR=0.513, 95% CI： 0.281～0.938）,而rs7025417 CC基因型是肠外表现的危险因素（P<0.05, OR=1.363, 95% CI： 1.006～1.846）;rs10118795 C等位基因降低肛周病变风险（P<0.05, OR=0.480, 95% CI： 0.232～0.994）,而rs10975519 CC基因型增加肛周病变风险（P<0.05, OR=2.054 , 95% CI： 1.053~4.009）;rs10975509 G等位基因是上消化道型CD的危险因素（P<0.05, OR=3.570, 95% CI： 1.328~9.600）,且其A等位基因携带者发生回结肠型CD的风险增加（P<0.05, OR=0.613, 95% CI： 0.377~0.996）;在治疗方面,rs10118795、rs10975509和rs7025417基因型均与CD患者英夫利昔单抗治疗后30周黏膜愈合相关（P<0.05,P<0.01,P<0.05）。UC患者中,未发现这8个SNP位点影响其临床表型（P>0.05）。结论：本研究中IL-33基因8个SNP位点不增加中国南方人群CD及UC发病风险,但部分位点影响CD的临床表型,某些SNP位点可能成为预测英夫利昔单抗疗效的标志物。     

Tankyrase 1 polymorphism associated with an increased risk in developing non-small cell lung cancer in a Chinese population: a proof-of-principle study

Objectives: Tankyrase 1 (TNKS1), a poly (ADP-ribose) polymerase, regulates telomere length and apoptosis in cells, overexpression of which occurred in non-small cell lung cancer (NSCLC). This study investigated TNKS1 single-nucleotide polymorphisms (SNPs) for association with a risk in NSCLC development in a Chinese population. Methods: NSCLC cases and healthy controls of 500 each were recruited for genotyping of 24 TNKS1 SNPs. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Haploview software was to analyze association between haplotypes and NSCLC risk. Results: TNKS1 rs6601328 A allele was associated with a lower risk in developing NSCLC and adenocarcinoma (ADC) (OR=0.71; 95% CI, 0.51-0.99 and OR=0.70; 95% CI, 0.50-0.99), whereas TNKS1 rs11991621 C allele (OR=1.44; 95% CI, 1.03-2.03), rs11991621 C/C (OR=1.44, 95% CI, 1.03-2.35; P=0.03), and rs10503380 G/G (OR= 1.56, 95% CI, 1.09-2.50, P=0.02) were associated with a higher risk in developing NSCLC or ADC in females and rs6601328 A/A major allele (OR=1.39; 95% CI, 1.00-1.92; P=0.047) and rs7015700 G/G (OR= 1.51, 95% CI, 1.04-2.21) was associated with an increased NSCLC or ADC risk in males but a reduced NSCLC risk (OR=0.63; 95% CI, 0.42-0.96) and ADC risk (OR=0.64; 95% CI, 0.42-0.97) in females. Haploview showed that there were three Haplotype Blocks associated with NSCLC risk. However, TNKS1 rs12541709 C/C was associated with protective effect against ADC (OR=0.75; 95% CI, 0.56-0.99; P=0.04) in this Chinese population. Conclusion: TNKS1 SNPs (rs11991621 rs10503380, and rs7015700) were associated with NSCLC risk, whereas rs6601328 and rs12541709 inversely associated with NSCLC or ADC risk in this Chinese population.     

The T244I variant of the interleukin-7 receptor-alpha gene and multiple sclerosis

Several but not all studies have provided evidence for the association between multiple sclerosis (MS) and the T244I variant of the interleukin-7 receptor-alpha gene (IL7RA), rs6897932. We performed a new replication case-control study in 599 MS patients and 594 healthy controls, all Caucasians from the south of Spain. The genotype and allele frequencies differed between MS cases and controls. The IL7RA rs6897932 C allele and the CC genotype were found to be factors for disease susceptibility [per allele odds ratio (OR) 1.32, 95% CI 1.1-1.6, P=0.0031; per CC genotype vs TT + TC genotypes, OR 1.5, 95% CI 1.18-1.87, P=0.0007]. The combined data analysis included 3324 cases and 5032 controls of Europeans and Americans of European origin resulting in stronger association with similar OR (P=1.9 x 10E-9). These findings in our sample support previous reported association studies between IL7RA rs6897932 and MS.     

Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development.     

Ischaemic stroke in hypertensive patients is associated with variations in the PDE4D genome region

Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies reported ambiguous findings. We examined 932 ischaemic stroke patients from a Swedish population-based stroke register, and 396 control subjects. We assessed possible associations between ischaemic stroke and nine preselected SNPs in the chromosome regions of the PDE4D gene, including rs12188950 (SNP45) and rs3887175 (SNP39); the ALOX5AP gene, including rs17222814 (SG13S25) and the promoter region of the MHC class II transactivator, MHC2TA. The T allele of SNP45 showed negative association with ischaemic stroke (odds ratio, OR=0.72; 95% confidence interval (CI): 0.58-0.91; P=0.0055). Among hypertensive subjects, this influence of the T allele of SNP45, and the T allele of SNP39, were more pronounced (with OR=0.52; 95% CI: 0.37-0.73; P=0.0001 and OR=0.57; 95% CI: 0.41-0.79; P=0.0007, respectively). These SNPs also interacted with hypertension with a relative excess risk due to interaction of -1.66 (P=0.0002) for SNP45 and -1.65 (P=0.0005) for SNP39. The P-values remained significant after correction for multiple testing. Among nonhypertensives, the A allele of SG13S25 indicated increased stroke risk (OR=1.82; 95% CI: 1.21-2.74; P=0.0039; not significant after Bonferroni correction). SNP45 was associated with ischaemic stroke even when controlling for hypertension, diabetes, heart disease and smoking. Our meta-analysis of 13 studies (including ours) showed no overall influence of SNP45 on ischaemic stroke. However, the 13 studies may differ because of nonrandom causes, as suggested by the heterogeneity test (P=0.042). This might support previously undetected mechanisms causing fluctuating ischaemic stroke risk.European Journal of Human Genetics (2008) 16, 1117-1125; doi:10.1038/ejhg.2008.62; published online 9 April 2008.     

IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis

To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1-2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan.     

Association of the CD226 single nucleotide polymorphism with systemic lupus erythematosus in the Chinese Han population

A novel non-synonymous (Gly307Ser) variant, rs763361, of the CD226 gene on chromosome 18q22 was recently shown to be associated with multiple autoimmune diseases. Taking into consideration that different autoimmune diseases may share some common pathogenic pathways, in this study we performed case-control studies to assess any genetic linkage with systemic lupus erythemtosus (SLE). An association between the Gly307Ser single nucleotide polymorphism (SNP) and susceptibility to SLE was identified. The TT genotype [odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.07-3.01, P = 0.025] and the T allele (OR = 1.34, 95% CI = 1.05-1.74, P = 0.018) of the rs763361 SNP were associated with the risk of SLE. This finding indicates that polymorphism of Gly307Ser (rs763361) in exon 7 of the CD226 gene may be associated with the development of SLE.     

A transmembrane polymorphism in FcgammaRIIb (FCGR2B) is associated with the production of anti-cyclic citrullinated peptide autoantibodies in Taiwanese RA

The aim of the current study was to determine whether the FcgammaRIIb 187-Ile/Thr polymorphism is a predisposition factor for subtypes of RA defined by disease severity and production of autoantibodies against cyclic citrullinated peptides (anti-CCPs) in Taiwanese RA patients. Genotype distributions and allele frequencies of FcgammaRIIb 187-Ile/Thr were compared between 562 normal healthy controls and 640 RA patients as stratified by clinical parameters and autoantibodies. Significant enrichment of 187-Ile allele was observed in RA patients positive for anti-CCP antibodies as compared with the anti-CCP negative RA patients (P=0.001, OR 1.652 (95% CI 1.210-2.257)) or as compared with the normal controls (P=0.005, OR 1.348 (95% CI 1.092-1.664)). In addition, 187-Ile allele was found to be enriched in RA patients positive for rheumatoid factor (RF) compared to the RF negative RA patients (P=0.024, OR 1.562 (95% CI 1.059-2.303)). Furthermore, the homozygotes were enriched in destructive male RA patients (P=0.035; OR 2.038 (95% CI 1.046-3.973)) and the 187-Ile allele was associated with early-onset of RA in Taiwanese patients (P=0.045, OR 1.548 (95% CI 1.007-2.379)). Thus, FcgammaRIIb SNP 187-Ile/Thr may influence the RA phenotypes in Taiwanese RA.     

Polymorphisms in the 5' region of the CD14 gene are associated with eczema in young children

BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene. OBJECTIVE: We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes. RESULTS: Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses. CONCLUSIONS: Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.