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首页> 外文期刊>PLoS Genetics >An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans
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An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

机译：CTLA4的非洲祖先特定等位基因赋予非洲裔美国人预防类风湿关节炎的保护作用

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Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ～1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10?26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p?=?2.4×10?28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF?=?0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations.
机译：细胞毒性T淋巴细胞相关蛋白4（CTLA4）是T细胞增殖的负调节剂。在欧洲血统的人群中，CTLA4的多态性与对类风湿性关节炎（RA）的敏感性不一致，但尚未在非裔美国人中进行检查。在欧洲和亚洲血统的大多数人口中，RA的患病率为〜1.0％。 RA在黑人非洲人中据称较少见，对其在非裔美国人中的患病率知之甚少。我们试图确定CTLA4多态性是否与非裔美国人的RA相关。我们使用Illumina和TaqMan平台对总共505名非洲裔美国RA患者和712名非洲裔美国对照组的CTLA4进行了12个单倍型标签单核苷酸多态性（SNP）的2期分析。 RA患者中rs231778 SNP的次要等位基因（G）为0.054，而对照组为0.209（4.462×10？26，Fisher精确）。 G等位基因的存在与RA的比值比（OR）大大降低有关（AG + GG基因型与AA基因型，或0.19，95％CI：0.13-0.26，p？=？2.4×10？ 28，费舍尔（Fisher）精确），暗示具有保护作用。该SNP在非洲人群中是多态的（约鲁巴人群中的次要等位基因频率[MAF] 0.09），但在其他人群中却很少见（在本研究的基因分型的530名白种人中，MAF？= 0.002）。在欧洲裔人口中与RA相关的标记（rs3087243 [+ 60C / T]和rs231775 [+ 49A / G]）在非洲裔美国人中未复制。在对HLA-DRB1共享表位进行分层，存在抗环瓜氨酸肽抗体或来自欧洲人群的混合程度之后，我们发现rs231778的关联没有混淆。非洲裔特定的CTLA4遗传变异似乎与非裔美国人免受RA侵袭有关。这一发现可能部分解释了非洲黑人人群中RA的患病率较低。

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