Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe
Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe
复制标题
DOI：
10.1038/sj.gene.6364370
复制
发表时间：
2007-03-01
影响因子：
5
通讯作者：
Gonzalez, A.
中科院分区：
文献类型：
--
作者：
Ferreiros-Vidal, I.;D'Alfonso, S.;Gonzalez, A.
我们从五个欧洲国家的种族匹配的系统性红斑狼疮 (SLE) 患者和对照中获得了 8 个 DNA 样本集合，总共 783 名患者和 1210 名对照。在对照组中发现了 PD1.3 A 等位基因频率的高度显着性变化，但在 SLE 患者中则没有。 PD1.3 A 等位基因的频率从欧洲东北部到西南部增加。当分析中包含其他五项 SLE 易感性研究的对照数据时，曲线明显明显（P = 1.2 x 10(-6)）。由于 SLE 患者缺乏平行变化，这种变异导致 SLE 关联研究存在严重偏差。因此，PD1.3 A 等位基因在欧洲东北部和中部地区的 SLE 患者中比对照中更常见，与东南欧的对照相似，但比欧洲大陆西南部的对照中出现频率较低。不同亚群中 SLE 患者和对照之间等位基因频率的这种分离表明，程序性细胞死亡 1 变异和疾病易感性不是独立的，但目前尚不清楚其关系类型。由于等位基因频率克隆在其他多态性中很常见，因此应仔细考虑它们对遗传流行病学研究的影响。
We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients. The frequency of the PD1.3 A allele increased from the Northeast to the Southwest of Europe. The cline was clearly apparent (P = 1.2 x 10(-6)) when data from controls of other five SLE susceptibility studies were included in the analysis. This variation has severely biased SLE association studies owing to the lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele was more common in SLE patients than in controls in the Northeast and Center of Europe, similar to controls in Southeast Europe, and less frequent than in the controls in the Southwest of the Continent. This dissociation in allele frequencies between SLE patients and controls in different subpopulations indicated that programmed cell death 1 variation and disease susceptibility are not independent but the type of relationship is currently unclear. As allele frequency clines are common in other polymorphisms their impact in genetic epidemiology studies should be carefully considered.