A. Ji, PhD, Research Fellow, C. Li, PhD, Professor, Shandong Provincial Key Laboratory of Metabolic Diseases, the Affiliated Hospital of Qingdao University, Qingdao, China.
A. Shaukat, MSc, Doctoral Student, M. Bixley, MSc, Assistant Research Fellow, M. Cadzow, PhD, Research Fellow, R.K. Topless, BSc, Assistant Research Fellow, T.J. Major, PhD, Research Fellow, A. Phipps-Green, MSc, Assistant Research Fellow, M.E. Merriman, BSc, Research Assistant, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
J Rheumatol. 2021 Nov;48(11):1736-1744. doi: 10.3899/jrheum.201684. Epub 2021 Jul 1.
The Māori and Pacific (Polynesian) population of Aotearoa New Zealand has a high prevalence of gout. Our aim was to identify potentially functional missense genetic variants in candidate inflammatory genes amplified in frequency that may underlie the increased prevalence of gout in Polynesian populations.
A list of 712 inflammatory disease-related genes was generated. An in silico targeted exome set was extracted from whole genome sequencing data in people with gout of various ancestral groups (Polynesian, European, East Asian; n = 55, 780, 135, respectively) to identify Polynesian-amplified common missense variants (minor allele frequency > 0.05). Candidate functional variants were tested for association with gout by multivariable-adjusted regression analysis in 2528 individuals of Polynesian ancestry.
We identified 26 variants common in the Polynesian population and uncommon in the European and East Asian populations. Three of the 26 population-amplified variants were nominally associated with the risk of gout ( [], OR = 1.28, = 0.03; [], OR = 1.37, = 0.002; [fibrinogen A alpha chain ()], OR = 1.34, = 0.02). The variant, within the established gout locus, was genetically independent of the association signal at SLC2A9.
We provide nominal evidence for the existence of population-amplified genetic variants conferring risk of gout in Polynesian populations. Polymorphisms in have previously been associated with gout in other populations, supporting our evidence for the association of this gene with gout.
新西兰的毛利人和太平洋（波利尼西亚）人群中痛风的患病率很高。我们的目的是确定在候选炎症基因中扩增的、可能具有功能的错义遗传变异体，这些变异体可能是导致波利尼西亚人群痛风患病率增加的原因。
生成了 712 个炎症性疾病相关基因的列表。从不同祖先群体（波利尼西亚、欧洲、东亚）的痛风患者的全基因组测序数据中提取了一个计算机靶向外显子组，以鉴定波利尼西亚扩增的常见错义变异体（次要等位基因频率>0.05）。通过多元调整回归分析，在 2528 名具有波利尼西亚血统的个体中，对候选功能变异体与痛风的相关性进行了测试。
我们确定了 26 个在波利尼西亚人群中常见而在欧洲和东亚人群中罕见的变异体。26 个人群扩增的变异体中有 3 个与痛风的风险呈名义相关（[]，OR=1.28，=0.03；[]，OR=1.37，=0.002；[]，纤维蛋白原 A 链（），OR=1.34，=0.02）。该变异体位于已建立的痛风基因座内，与 SLC2A9 关联信号在遗传上是独立的。
我们提供了名义证据，证明在波利尼西亚人群中存在扩增的遗传变异体，这些变异体赋予了痛风的风险。在其他人群中， 中的多态性与痛风有关，这支持了我们关于该基因与痛风有关的证据。
