Butler Faven, Alghubayshi Ali, Roman Youssef
Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, Smith Building, Rm 334, Richmond, VA 23298-0533, USA.
J Pers Med. 2021 Mar 22;11(3):231. doi: 10.3390/jpm11030231.
Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: (rs2231142), (rs734553), (rs1183201), (rs1171614), (rs1260326), (rs2078267) (rs505802) (rs3741414) (rs675209) (rs12129861), and (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher's Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.
痛风是一种由血清尿酸盐（SU）升高引起的炎症性疾病，这种情况被称为高尿酸血症（HU）。包括单核苷酸多态性（SNP）在内的基因变异可改变尿酸转运蛋白的功能，导致不同人群中HU和痛风的患病率存在差异。在美国，痛风患病率对某些种族群体有不同影响。本拟议分析的目的是比较欧洲人（EUR）与以下主要种族群体之间尿酸相关遗传风险等位基因的频率：来自千人基因组计划的美国西南部非洲人（ASW）、汉族（CHS）、日本人（JPT）和墨西哥人（MXL）。利用千人基因组计划的Ensembl基因组浏览器，对11个基因中的11个SNP进行跨群体等位基因频率比较，这些基因在生理上与SU水平和痛风风险相关且具有显著关联。基因/SNP对包括：（rs2231142）、（rs734553）、（rs1183201）、（rs1171614）、（rs1260326）、（rs2078267）（rs505802）（rs3741414）（rs675209）（rs12129861）和（rs478607）。在适当情况下，使用卡方检验或费舍尔精确检验将等位基因频率与EUR进行比较。采用Bonferroni多重比较校正，P<0.0045具有统计学意义。风险等位基因定义为与基线或更高的HU和痛风风险相关的等位基因。估计了每个群体中11个SNP的累积HU或痛风风险等位基因指数。利用已发表的流行病学数据和文献综述评估美国和非美国人群中HU和痛风的患病率。与EUR相比，ASW中7/11、MXL中9/11、JPT中9/11以及CHS中11/11的SNP频率存在显著差异。ASW、MXL、CHS和JPT的HU或痛风风险等位基因指数分别为5、6、9和11。在11个SNP中，CHS和JPT中风险等位基因的百分比为100%。与非美国人群相比，西方世界国家中HU和痛风的患病率似乎更高。与EUR相比，CHS和JPT人群的HU或痛风风险等位基因频率最高，其次是MXL和ASW。这些结果表明，亚洲血统个体患HU和痛风的风险更高，这可能部分解释了在门诊护理环境中，亚洲人痛风患病率比白种人高出近三倍的原因。此外，痛风仍然是一种在发达国家中明显呈全球上升趋势的疾病。
