Sanchez Elena, Webb Ryan D, Rasmussen Astrid, Kelly Jennifer A, Riba Laura, Kaufman Kenneth M, Garcia-de la Torre Ignacio, Moctezuma Jose F, Maradiaga-Ceceña Marco A, Cardiel-Rios Mario H, Acevedo Eduardo, Cucho-Venegas Mariano, Garcia Mercedes A, Gamron Susana, Pons-Estel Bernardo A, Vasconcelos Carlos, Martin Javier, Tusié-Luna Teresa, Harley John B, Richardson Bruce, Sawalha Amr H, Alarcón-Riquelme Marta E
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Arthritis Rheum. 2010 Dec;62(12):3722-9. doi: 10.1002/art.27753.
To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).
Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.
A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.
Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.
评估基因决定的美洲印第安人血统是否预示系统性红斑狼疮（SLE）已知易感基因的风险等位基因出现频率增加。
对804名混血狼疮患者和667名混血健康对照者进行16个已确认的SLE遗传易感位点内的单核苷酸多态性（SNP）基因分型。此外，对347个混合信息标记进行基因分型。使用STRUCTURE确定个体血统比例。使用PLINK进行关联分析，并使用线性回归分析血统与风险等位基因出现之间的相关性。
对不同人群中16个SNP的遗传关联进行的荟萃分析表明，在富含欧洲和美洲印第安人血统的西班牙裔混血队列中，TNFSF4、STAT4、ITGAM和IRF5与狼疮相关。此外，主要组织相容性复合体区域内的2个SNP，先前在欧洲人的全基因组关联研究中显示与狼疮相关，在混血人群中也与狼疮相关。使用线性回归，我们预测，将100%美洲印第安人血统的SLE患者与0%美洲印第安人血统的SLE患者进行比较时，风险等位基因平均增加2.34个（P < 0.0001）。预计美洲印第安人血统多43%的SLE患者会多携带1个风险等位基因。
我们的结果表明，美洲印第安人血统与SLE风险等位基因数量增加相关。
