Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Genes Immun. 2012 Apr;13(3):232-8. doi: 10.1038/gene.2011.82. Epub 2011 Dec 22.
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.
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，其特征是自身抗体的产生和器官损伤。狼疮肾炎（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）和邻近载脂蛋白 L1（APOL1）基因变异之间的关联。我们评估了跨越 MYH9 的 167 个变异与多民族样本中 LN 的关联。还在欧洲裔美国人（EA）（N=579）和非裔美国人（AA）（N=407）中测试了 APOL1 中两个先前确定的风险变异与 LN 的关联。在 EA（N=4620）中，LN 与 MYH9 之间观察到多个超过 Bonferroni 校正 P 值<2.03×10(-3)的关联峰，其中 rs2157257 最明显（P=4.7×10(-4)，优势比（OR）=1.205）。在 Gullah 人群中也检测到与 MYH9 相关的适度效应（rs8136069，P=0.0019，OR=2.304）。在 AA、亚洲人、美洲原住民或西班牙裔中未发现 LN 与 MYH9 之间存在关联。这项研究首次调查了非非洲裔人群中 MYH9 在 LN 中的作用，以及任何人群中 APOL1 在 LN 中的作用，并为 EA 中 MYH9 在 LN 中的潜在作用提供了新的见解。
