Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.
Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.
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DOI：
10.1038/gene.2011.82
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发表时间：
2012-04
影响因子：
5
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系统性红斑狼疮(SLE)是一种以自身抗体产生和器官损害为特征的复杂自身免疫性疾病。狼疮性肾炎(LN)是SLE最严重的表现之一。多项研究报道了肾脏疾病与非肌肉肌球蛋白重链9(MyH9)和邻近的载脂蛋白L 1(APOL1)基因变异的相关性。我们在一个多种族样本中评估了167个跨越Myh9的变异与LN的关联。在欧洲裔美国人(EAs)(N=579)和非裔美国人(AAs)(N=407)中，也测试了APOL1中先前发现的两个风险变异体与LN的相关性。在EAS中，LN和Myh9之间有多个关联峰超过P<；2.03×10−3的Bonferroni校正p值(N=4620)，其中最显著的关联位于rs2157257(p=4.7x10−4；优势比[OR]=1.205)。Myh9对古拉的影响也不大(rs8136069，p=0.0019，OR=2.304)。在AAS、亚洲人、美洲印第安人或西班牙人中未发现LN和Myh9之间的关联。这项研究首次对非非洲人LN中的Myh9和任何人群中的LN中的APOL1进行了研究，并对Myh9在LN中在EAS中的潜在作用提出了新的见解。
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected p-value of p < 2.03 × 10−3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (p = 4.7 × 10−4; odds ratio [OR]=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, p = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population and presents novel insight into the potential role of MYH9 in LN in EAs.