An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts
An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts
复制标题
DOI：
10.1210/clinem/dgaa347
复制
发表时间：
2020-09-01
影响因子：
5.8
通讯作者：
Mitchell, Anna Louise
中科院分区：
文献类型：
--
作者：
Lane, Laura Claire;Kus, Aleksander;Mitchell, Anna Louise
研究背景：Graves病（GD）的遗传背景在很大程度上仍不清楚。人类白细胞抗原（HLA）复合物P5（HCP 5）中的内含子变异体先前已与波兰患者队列中的GD易感性和发病年龄相关。目的：我们旨在调查HCP 5变异体rs3094228与英国队列中的GD易感性和发病年龄的相关性，并对英国和波兰数据进行荟萃分析。设计和参与者：使用Taqman化学法对469例英国GD患者的rs3094228进行基因分型。基因型频率进行了比较，从威康信托病例对照财团使用逻辑回归分析的基因型数据。为了确定rs3094228是否与GD发病年龄独立相关，还对HLA DRB 1 *0301标签变体rs 535777进行了基因分型。（P-等位基因=5.08 x 10（-9），比值比1.76; [95%置信区间，1.46-2.13]）。这种关联在晚发型GD中更为显著（
Context: The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients.Objective: We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data.Design and Participants: rs3094228 was genotyped in 469 UK patients with GD using Taqman chemistry. Genotype frequencies were compared with genotypic data available from the Wellcome Trust casecontrol consortium using logistic regression analysis. To determine whether rs3094228 is independently associated with age of GD onset, the HLA DRB1*0301 tagging variant, rs535777, was also genotyped.Results: The C allele of rs3094228 was overrepresented in the UK GD cohort compared with controls (P-allele=5.08 x 10(-9), odds ratio 1.76; [95% confidence interval, 1.46-2.13]). This association was more marked in young-onset GD (