RANTES promoter polymorphism as a genetic risk factor for rheumatoid arthritis in the Chinese

OBJECTIVES: There is increasing evidence suggesting a role of RANTES in the pathogenesis of rheumatoid arthritis (RA) and we evaluated the possible effect of RANTES gene on the susceptibility to RA in Chinese patients. METHODS: We examined the polymorphisms at the promoter positions -28 and -403 of this gene in 151 Chinese RA patients and 149 ethnically matched healthy controls. RESULTS: The genotypic frequencies in this study were in Hardy-Weinberg equilibrium. RA patients had significantly higher frequencies of the A allele (36.1% vs. 27.5%, p = 0.024) and A/A genotype (odds ratio [OR] = 3.3, 95% confidence interval [CI] = 1.4-7.9, p = 0.005) at the promoter -403 position. Differences in allele and genotype frequencies at the promoter -28 position between patients and controls were not statistically significant (for G allele, p = 0.103 and for genotype, p = 0.106). RA patients also had a significantly higher frequency of the -28 C/G with -403 A/A compound genotype (OR = 4.6, 95% CI = 1.5-14.5, p = 0.005), and a higher frequency of the -28 G/-403 A haplotype with marginal statistical significance (OR = 1.7, 95% CI = 1.0-3.1, p = 0.059). CONCLUSION: Our results indicate that polymorphism in the promoter region of RANTES gene is associated with the susceptibility to RA in the Chinese population.     

HHIP基因rs13118928单核苷酸多态性与慢性阻塞性肺疾病易感性的荟萃分析

目的探讨Hedgehog相互作用蛋白(HHIP)基因rs13118928位点单核苷酸多态性与慢性阻塞性肺疾病(COPD)易感性的关联。 方法系统检索PubMed、EMBASE、Web of Science、中国知网和万方五个电子数据库。检索时间为建库到2018年1月5日,根据制定的纳入标准筛选出相关研究文章,提取数据后利用RevMan5.3软件进行统计分析,计算出各种遗传模型下的比值比(OR)和95%的可信区间(95%CI)。 结果本项研究共纳入7篇文献,包括5 157个COPD患者和9 768个健康对照者。荟萃分析结果显示HHIP基因rs13118928多态性在五种遗传模型下均与COPD有显著相关性：A vs. G,OR＝1.14,95%CI,1.08～1.20,P<0.001;AA vs. GG,OR＝1.36,95%CI,1.20～1.55,P<0.001;AG vs. GG,OR＝1.27,95%CI,1.03～1.58,P＝0.030;AA+AG vs. GG,OR＝1.31,95%CI,1.10～1.57,P＝0.003;AA vs. AG+GG,OR＝1.12,95%CI,1.04～1.21,P＝0.002。亚组分析结果显示在亚洲人种和高加索人种中,rs13118928多态性在A vs. G和AA vs. GG遗传模型下与COPD的发生有显著相关性。 结论HHIP基因rs13118928单核苷酸多态性与COPD的发生有显著相关性。A等位基因和AA基因型携带者对COPD有较高的易感性。     

CTLA-4 gene polymorphism in Japanese patients with rheumatoid arthritis

OBJECTIVE: To examine whether CTLA-4 gene confers susceptibility to rheumatoid arthritis (RA) in Japanese. METHODS: We investigated the distribution of a CTLA-4 gene polymorphism in 85 Japanese patients with RA and 200 controls. An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The patients were also analyzed with respect to HLA-DR status. HLA-DR typing was performed by PCR sequence-specific oligonucleotide typing. RESULTS: The distribution of genotype frequencies differed between RA and controls (chi-squared 8.63, 2 df, p = 0.013). The CTLA-4 AG genotype occurred more frequently in patients with RA (59 vs 44%), and the presence of at least one G allele (GG or AG) conferred an odds ratio of 2.53 (95% CI 1.74-3.32). When the patients were analyzed with respect to HLA-DR status, this association was restricted to patients carrying the susceptible HLA allele (HLA-DRB1*0405). CONCLUSION: The CTLA-4 gene is associated with Japanese patients with RA carrying the susceptible HLA allele.     

IL13RA2 gene polymorphisms are associated with systemic sclerosis

OBJECTIVE: To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION: Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease.     

Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand,foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies

Background:Several case-control studies have been conducted on the relationship between rs3775290 C/T and rs3853839 C/G single nucleotide polymorphisms of the Toll-like receptor (TLR) gene and hand, foot, and mouth disease (HFMD) susceptibility and severity. This meta-analysis aimed to offer a systemic review of HFMD susceptibility and severity among the Chinese Han population associated with the C/T (rs3775290) polymorphism of the TLR3 gene or C/G (rs3853839) polymorphism of the TLR7 gene.Methods:A computer search was conducted using PubMed, Web of Science, Embase, CNKI, CBM, VIP, and WanFang databases. The time ranges were from database establishment to 30/7/2021. Articles selected according to the inclusion and exclusion criteria underwent data extraction and methodological quality evaluation. RevMan 5.4 and Stata 16.0 were adopted for meta-analysis, and the incorporated odds ratio (OR) values and 95% confidence intervals (CIs) were calculated. Sensitivity and publication bias assessments were performed.Results:8 articles with 9 studies were selected. Among them, there were 858 cases and 577 controls in TLR3 rs3775290 studies as well as 2151 cases and 1554 controls in TLR7 rs3853839 studies. Regarding rs3775290 of TLR3, susceptibilities of the severe type of T-possessing individuals were larger than those of C-possessing individuals [OR = 1.34, 95%CI (1.10, 1.64), P = .004]. The susceptibility of individuals with the severe TT genotype was 1.61 times that of individuals with the CC genotype [95%CI (1.07, 2.43), P=0.02], while susceptibility to HFMD was not influenced by the genotype. In terms of the rs3853839 of the TLR7 gene, C allele carriers have a higher risk of developing HFMD than G allele carriers. The susceptibility to HFMD in CC+CG individuals was 1.24 times than that in GG individuals [95%CI (1.07, 1.43), P = .004]. However, no relationship was found between this polymorphism and severity of the severe type. No significant publication bias was observed in this study.Conclusions:rs3775290 (C/T) of TLR3 is associated with susceptibility to the severe type, whereas rs3853839 (C/G) of TLR7 is associated with susceptibility to HFMD. However, owing to the limited quantity and quality of the research, the aforementioned conclusions are yet to be justified by more high-quality research.     

CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis—results and the review of the literature

Autoimmune thyroid diseases frequently overlaps with rheumatoid arthritis (RA). Among genetic factors, the role of the HLA antigens and CTLA4 gene polymorphisms in the overlapping has been suggested. The aim of this study was to investigate the alleles and genotypes frequency of the CTLA4 exon1 A49G polymorphism in Slovak patients with RA, Hashimoto thyroiditis (HT), both (RA + HT) and in healthy controls. Fifty-seven unrelated adults with RA, 57 patients with HT, 34 patients with both (RA + HT), and 51 normal subjects were studied. All were ethnic Slovaks living in the same geographical area. The CTLA4 exon1 A49G polymorphism was genotyped by using small amplicon melting analysis after real-time PCR. The CTLA4 49GG genotype and G allele frequency in the group with RA was not significantly higher in comparison with controls (10.53% vs. 9.8%, p = 0.62, OR 1.39, 95% CI 0.35–5.74 and 39.47% vs. 34.31%, p = 0.43, OR 1.25, 95% CI 0.72–2.18). The frequency of GG genotype was slightly but not significantly higher in patients with HT as compared with control group (19.3% vs. 9.8%, p = 0.17, OR 2.27, 95% CI 0.67–8.45). However, the frequency of GG genotype and G allele in patients with both RA and HT was significantly higher than that in controls (29.41% vs. 9.8%, p = 0.02, OR 4.49, 95% CI 1.20–18.54 and 51.47% vs. 34.31%, p = 0.03, OR 2.02, 95% CI 1.08–3.81). The frequency of GG genotype of CTLA4 A49G gene polymorphism in Slovak patients with RA is not significantly higher in comparison to control group. However, carriers of GG genotype with RA may be susceptible to develop HT.     

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.     

-449 C>G polymorphism of NFKB1 gene,coding nuclear factor-kappa-B,is associated with the susceptibility to ulcerative colitis

AIM: To clarify the association between a polymorphism -449 C>G (rs72696119) in 5’-UTR of NFKB1 with ulcerative colitis (UC).METHODS: The studied population comprised 639 subjects, including patients with UC (UC cases, n = 174) and subjects without UC (controls, n = 465). We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS: The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%, respectively (P = 0.10). Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls (P = 0.017), and the GG homozygote was significantly associated with susceptibility to UC [odds ratio (OR), 1.88; 95%CI, 1.13-3.14]. In male subjects, the GG homozygote was associated with an increased risk for UC (OR, 3.10; 95%CI, 1.47-6.54; P = 0.0053), whereas this association was not found in female subjects. In addition, the GG homozygote was significantly associated with the risk of non-continuous disease (OR, 2.06; 95%CI, 1.12-3.79; P = 0.029), not having total colitis (OR, 2.40; 95%CI, 1.09-3.80, P = 0.040), disease which developed before 20 years of age (OR, 2.80; 95%CI, 1.07-7.32, P = 0.041), no hospitalization (OR, 2.28; 95%CI, 1.29-4.05; P = 0.0090) and with a maximum of 8 or less on the UCDAI score (OR, 2.45; 95%CI, 1.23-4.93; P = 0.022).CONCLUSION: Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC. This polymorphism influences the susceptibility to and pathophysiological features of UC.     

Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis

Up to now, many publications have evaluated the correlation between IL-23R polymorphisms and ankylosing spondylitis with conflicting results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of IL-23R polymorphisms with AS. Relevant published data were retrieved through Medline, PubMed, Embase, Web of Science, CNKI, Chinese BioMedical Literature Database on disc, and the statistical analysis was conducted using Stata 11.0. (1) A total of 11 literatures, including 13 population samples, were studied. (2) The allele A frequency of rs11209032 was higher in the AS group than in the controls (A vs. G: OR = 1.173, 95% CI = 1.107-1.243, P < 0.001). (3) The allele A of rs1004819 was higher in the AS group than in the controls in both all-pooled population (A vs. G: OR = 1.147, 95% CI = 1.022-1.287, P = 0.02) and Europe-pooled population (A vs. G: OR = 1.199, 95% CI = 1.007-1.429, P = 0.042). (4) The allele frequency T of rs1343151, G of rs10489629, and A of rs11209026 was lower in the AS group than in the controls. (5) No significant differences were found in allele frequency of rs10889677 polymorphism between cases and controls by random effects model. We concluded that the genetic susceptibility for AS is associated with the IL-23R gene polymorphisms. The protective SNPs include rs1343151, rs10489629, and rs11209026 while rs1004819 and rs11209032 may be the susceptibility SNPs.     

肿瘤坏死因子-α-308位点多态性与东亚人群类风湿关节炎相关性的Meta分析

目的 Meta分析肿瘤坏死因子(TNF)-α-308位点多态性与东亚人群类风湿关节炎(RA)的相关性.方法 在PubMed、Ebsco、中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库中查询TNF-α-308位点多态性与东亚人群儿A相关性的文献.用Meta分析的方法分析基因型AA与GG,GA与GG,AA与GG+GA,GA+AA与GG,A与G在RA组与健康对照组中是否存在差异.结果 共纳入4篇文献进入本研究(957例RA患者,1196名健康对照).对总体东亚人群进行Meta分析,发现TNF-α-308A与RA呈负相关[优势比(OR)=0.36,95%可信区间(CI)=0.16～0.80,P=0.01];将人群按照种族分层,发现TNF-α-308A与中国人群RA呈负相关(OR=0.40,95%CI=0.16～1.01,P=0.05).结论 TNF-α-308位点等位基因和基因型与东亚及中国人群RA呈负相关.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG?+?GG: OR 0.48, 95% CI 0.39-0.59; TT?+?TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.     

白细胞介素-7受体α基因多态性对亚洲人多发性硬化易感性的影响

目的 探讨亚洲人群白细胞介素-7受体α(IL-7RA)基因rs6897932多态性位点与多发性硬化(MS)遗传易感性的关系。 方法 采用反转录聚合酶链反应(RT-PCR)技术,对78例MS和视神经脊髓炎( neuromyelitis optica,NMO)患者(NMO组),187非MS的视神经脊髓炎(non-NMO MS)患者（non-NMO MS组）及158例健康对照组筛查IL-7RA基因分布频率,并进行统计学分析。结果 non-NMO MS组C等位基因频率89.3％（167例）明显高于对照组79.8％（126例）,差异有统计学意义(OR=2.12,95％CI:1.38～3.25,P＜0.01);CC等位基因型频率分别为78.6％( 147例)与63.3％（100例）,差异有统计学意义(OR=2.13,95％CI;1.32～3.43,P＜0.01);而NMO组与对照组C、CC等位基因频率比较,差异无统计学意义。 结论 IL-7RA基因rs6897932多态性位点影响亚洲人群MS遗传易感性。C等位基因为MS的易感因子,T等位基因则可能为MS的保护因子。     

TGF-β1 +869T/C (rs1982073) gene polymorphism and susceptibility to rheumatoid arthritis: Updated systematic review and meta-analysis

Rheumatoid arthritis (RA) is a complex autoimmune disease that affects about 1% of the world's population. The conclusions about the relationship between TGF gene polymorphism and the risk of RA are still inconsistent. Therefore, we performed a meta-analysis to re-evaluate the relationship between TGF-β1 T869C gene polymorphism and the risk of rheumatoid arthritis.Method: We performed a systematic electronic search in PubMed, Embase, Elsevier, Web of Science, Cochrane Library, Medline and China National Knowledge Infrastructure database (up to August 2020). In the subgroup analysis, we divide the research into three groups: Asian, European and Mediterranean, The combined OR and 95%CI of the five models (allele model, homozygous model, heterozygous model, dominant model, recessive model) were calculated, respectively.Results: 15 case-control studies (14 articles) were involved in this meta-analysis, including 2103 cases and 2143 healthy controls. In the overall analysis, it showed that there may be an significant association between TGF-β1+869T/C polymorphism and RA sensitivity (allele model, T vs. C: OR=1.444, 95% CI=1.171-1.782, P=0.001; homozygous model, TT vs. CC: OR=1.910, 95% CI=1.322-2.761, P=0.001; heterozygous model, CT vs. CC: OR=1.558, 95% CI=1.179-2.059,P=0.002; dominant model, TT+CT vs. CC: OR= 1.742, 95% CI=1.303-2.329, P=0.001; recessive model, TT vs. CT+CC: OR=1.400, 95% CI= 1.058-1.852, P=0.018).However, the results of ethnic subgroup analysis indicated that rs1982073 was not associated with RA risk in Europeans(allele model, T vs. C: OR=0.993, 95% CI=0.849-1.162, P=0.931, I² <0.1%, P>0.1).Conclusion: In summary, our meta-analysis showed that the rs1982073 T allele does not increase RA susceptibility in Europeans.     

The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis

Integrin αvβ3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin α_V (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet’s disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6–3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3–3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1–7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p _ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.     

Positive association of the HLA DMB1*0101-0101 genotype with rheumatoid arthritis.

OBJECTIVE: HLA DM is a non-classical major histocompatibility complex (MHC) class II molecule that has been shown to facilitate peptide loading with classical class II molecules. METHODS: In this study, we analysed the polymorphism in exon 3 of HLA DMA and DMB genes by a polymerase chain reaction-sequence-specific oligonucleotide probe method in 163 rheumatoid arthritis (RA) patients and 146 ethnically matched controls. The HLA-DRB1 genotype was also analysed by a reverse-dot blot method. RESULTS: Our results show in RA patients a significant increase in the HLA DMB*0101 allele frequency (83% vs 72.3% of the controls, P < 1.6 x 10(-3), significance at P < 0.0125) and in the HLA DMB*0101-0101 homozygote genotype frequency [70.8% vs 50% of the controls, P < 4.2 x 10(-4), significance at P < 0.00625, odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.43-4]. The increase in DMB*0101 allele and homozygote genotype frequencies was independent of a linkage disequilibrium between DMB and DRB1 alleles. The analysis of non-random associations between the HLA-DM and DRB1 alleles only revealed a significant association in controls between DMB*0104 and DRB1*07 alleles (delta = 0.01, P < 7 x 10(-4), significance at P < 9.6 x 10(-4)). On the other hand, the DMB*0101-0102 genotype frequency was increased in DRB1*0401-negative RA patients as compared to controls (11% vs 2%, P < 0.011, significance at P < 0.015, OR = 6.2, 95% CI: 1.2-30). CONCLUSION: Our data suggest that HLA-DM alleles could play a role in the genetic susceptibility to RA.     

An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies

OBJECTIVE: To examine the allelic association of the single nucleotide polymorphism (CTLA4A/G) in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA4) gene with early rheumatoid arthritis (RA). METHODS: One hundred and twenty-three unrelated white probands with early RA from the north-east of England and 349 local ethnically matched controls were studied. The CTLA4A/G polymorphism was genotyped with a polymerase chain reaction (PCR) method and digestion with the restriction enzyme Bst71I. Probands were also screened by allele-specific PCR for alleles HLA DRB1*01 and DRB1*04. RESULTS: The frequency of the G allele at CTLA4A/G was significantly increased in probands with early RA compared with controls [43 vs 36%; P=0.028, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82]. Most of this increased frequency was attributable to RA individuals with coexisting autoimmune thyroid disease or type 1 diabetes (58 vs 36% in controls; P=0.005, OR 2.50, CI 1.29-4.84). The frequency of the G allele in RA patients without autoimmune endocrinopathy was 40%, which was not significantly different from that in controls (P=0.140). CONCLUSION: The association between the CTLA4 G allele and early RA is largely explained by individuals with RA who have coexisting autoimmune endocrinopathies.     

Association of STAT4 with rheumatoid arthritis: a replication study in three European populations

OBJECTIVE: This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. METHODS: Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single-nucleotide polymorphism rs7574865 using a TaqMan 5'-allele discrimination assay. The chi-square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09-1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03-1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21-1.73]). The overall P value for all 3 populations was 9.79 x 10(-6) (OR 1.25 [95% CI 1.13-1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies was observed. A meta-analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19-1.33) (P = 1 x 10(-5)). CONCLUSION: Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.     

男性早发性冠心病与血管紧张素原基因启动子区域-217G/A和-152G/A多态

目的:研究血管紧张素原(angiotensinogen,AGT)基因启动子区域的-217G/A和-152G/A多态与上海地区汉族男性早发性冠心病(CAD)的相关性。方法:采用多重SNaPshot反应,在100例男性早发性CAD患者和100名健康男性对照者中,对AGT基因启动子区域的-217G/A和-152G/A多态进行基因分型。结果:-217G/A多态AA、AG和GG基因型在CAD组中的分布与对照组相比有显著性差异(P=0.039),CAD组的A等位基因频率较对照组亦显著增加(P=0.012),A等位基因携带者早发性CAD的发病危险是非携带者的1.913倍(95%CI1.151～3.182)。-152G/A多态的基因型分布在2组间的差异无统计学意义(P=0.154),其A、G等位基因频率2组相比有差异(P=0.044)。在多支病变组中,-217G/A多态的基因型分布及其等位基因频率2组相比均有显著性差异(分别为P=0.010和P=0.005),且A等位基因携带者发生多支病变的危险是非携带者的2.307倍(95%CI1.274～4.179)。结论:在上海地区的汉族男性人群中,AGT基因-217G/A和-152G/A多态可能是其早发性CAD的遗传性危险因素,且-217G/A多态可能还与冠状动脉粥样硬化的病变程度相关。     

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between the tagging single nucleotide polymorphism sites(tagSNPs)of the Interleukin-18(IL-18)gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.METHODS:Five hundred and one cases of chronic hep-atitis B virus(HBV)infection and 301 HBV natural clearance controls were studied.Two tagSNPs in the IL-18 gene(rs1946518A/C and rs574424C/G)were genotyped by the Multiplex Snapshot technique.The genotype and allele frequencies were calculated and analyzed.RESULTS:In the genotypes of rs1946518,the AA type was present at a higher frequency in the patients compared to those in the controls.Odds ratio(OR)of theAA genotype for the comparison with that of the AC and the CC genotype was 1.537(95%confidence intervals(CI):1.116-2.218,P=0.009<0.025).In pheno-types,the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls(P=0.017<0.025).OR of the allele A for the comparison with that of the allele C was 1.279(95%CI:1.045-1.567).As for the rs574424 genotypes,no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed.No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed.CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene.However,no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.     

Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary biliary cirrhosis: a systematic review

Background and Aim: The cytotoxic T‐lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed on activated and regulatory T lymphocytes. Polymorphisms could have remarkable effects on susceptibility to autoimmunity. However, the associations between CTLA‐4 polymorphisms and primary biliary cirrhosis (PBC) remain ambiguous. The aim of this meta‐analysis is to determine more precise estimations of the relationship. Methods: From literature retrieval from PubMed, Web of Science, Science Direct, and the Chinese National Knowledge Infrastructure (CNKI) Database, the publications on the associations between rs231775, rs3087243, rs5742909, rs231725 and rs11571317 polymorphisms of CTLA4 and PBC through June 2011 were collected. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in fixed or random model, I² was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Revman 5.1 and Stata 11. Results: Overall, a significantly increased risk was found for G versus A allele for rs231775 (OR = 1.28, 95% CI = 1.17–1.41). For rs3087243, a significant association was found for AA versus GG genotype (OR = 0.66; 95% CI = 0.55–0.80). When subgroup analysis by ethnicity was performed, the same association was only found in Caucasians. For rs231725, the OR values (95% CI) for GG versus AA, GA versus AA and G versus A allele were 0.52 (0.40–0.68), 0.74 (0.60–0.92) and 0.73 (0.61–0.88). No significant associations were found for other polymorphisms. Conclusion: The G allele of rs231775 is a risk factor for PBC, while AA genotype of rs3087243 and GG, GA and G allele of rs231725 show negative associations with PBC.