Namjou B, Gray-McGuire C, Sestak A L, Gilkeson G S, Jacob C O, Merrill J T, James J A, Wakeland E K, Li Q-Z, Langefeld C D, Divers J, Ziegler J, Moser K L, Kelly J A, Kaufman K M, Harley J B
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Genes Immun. 2009 Jul;10(5):517-24. doi: 10.1038/gene.2009.33. Epub 2009 May 14.
Complement cascade plasma proteins play a complex role in the etiopathogenesis of systemic lupus erythematosus (SLE). Hereditary C1q deficiency has been strongly related to SLE; however, there are very few published SLE studies that evaluate the polymorphisms of genes encoding for C1q (A, B and C). In this study, we evaluated 17 single nucleotide polymorphisms (SNPs) across 37 kb of C1QA, C1QB and C1QC in a lupus cohort of individuals of the African-American and Hispanic origin. In a case-only analysis, a significant association at multiple SNPs in the C1QA gene was detected in African Americans with kidney nephritis (best P=4.91 x 10(-6)). In addition, C1QA was associated with SLE in African Americans with a lack of nephritis and accompanying photosensitivity when compared with that in normal controls (P=6.80 x 10(-6)). A similar trend was observed in the Hispanic subjects (P=0.003). Quantitative analysis showed that some SNPs in C1q genes might be correlated with C3 complement levels in an additive model among African Americans (best P=0.0001). The C1QA gene is associated with subphenotypes of lupus in the African-American and Hispanic subjects. Further studies with higher SNP densities in this region and other complement components are necessary to elucidate the complex genetics and phenotypic interactions between complement components and SLE.
补体级联血浆蛋白在系统性红斑狼疮（SLE）的发病机制中发挥着复杂作用。遗传性C1q缺乏与SLE密切相关；然而，很少有已发表的SLE研究评估编码C1q（A、B和C）的基因多态性。在本研究中，我们评估了非裔美国人和西班牙裔狼疮队列中跨越C1QA、C1QB和C1QC 37 kb的17个单核苷酸多态性（SNP）。在仅病例分析中，在患有肾炎的非裔美国人中检测到C1QA基因多个SNP存在显著关联（最佳P = 4.91×10⁻⁶）。此外，与正常对照相比，在无肾炎且伴有光敏性的非裔美国人中，C1QA与SLE相关（P = 6.80×10⁻⁶）。在西班牙裔受试者中也观察到类似趋势（P = 0.003）。定量分析表明，在非裔美国人中，C1q基因的一些SNP可能与补体C3水平呈加性模型相关（最佳P = 0.0001）。C1QA基因与非裔美国人和西班牙裔受试者中狼疮的亚表型相关。需要进一步研究该区域及其他补体成分中更高密度的SNP，以阐明补体成分与SLE之间复杂的遗传学和表型相互作用。
