Ramos Paula S, Shaftman Stephanie R, Ward Ralph C, Langefeld Carl D
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Autoimmune Dis. 2014;2014:203435. doi: 10.1155/2014/203435. Epub 2014 Jan 23.
The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, including PTPN22, TNFSF4, TET3-DGUOK, TNIP1, UHRF1BP1, BLK, and ITGAM genes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles.
系统性红斑狼疮（SLE）患病率的种族差异以及人群中SLE风险等位基因相对较高频率的原因尚未完全明确。诸如自然选择等群体遗传因素会在多代人中改变等位基因频率，这可能有助于解释此类常见风险变异在人群中的持续存在以及SLE的差异风险。为了更好地理解可能归因于自然选择的SLE遗传基础，我们使用群体分化、等位基因频率和基于单倍型的检测方法，在HapMap和HGDP人群中，对总共74个有确凿证据表明与SLE相关的基因组区域进行了近期正选择证据的检测。在几个与SLE相关的基因座上，包括PTPN22、TNFSF4、TET3 - DGUOK、TNIP1、UHRF1BP1、BLK和ITGAM基因，在不同研究和统计方法中均观察到了一致的正选择迹象。本研究首次评估并报告了几个与SLE相关的区域显示出正自然选择的迹象。这些结果提供了确凿证据，支持近期正选择作为SLE风险基因座人群频率升高的一种潜在机制，并支持未来整合自然选择信号以帮助识别功能性SLE风险等位基因的研究。
