Alghubayshi Ali, Edelman Alison, Alrajeh Khalifa, Roman Youssef
Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298-0533, USA.
Department of Obstetrics and Gynecology, School of Medicine, Oregon Health Science University, Portland, OR, 97239, USA.
BMC Rheumatol. 2022 Jan 6;6(1):1. doi: 10.1186/s41927-021-00239-7.
Gout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)-high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples.
The biospecimens repository at the University of Hawai'i provided DNA samples of consented post-partum women of Japanese, Filipino, Korean, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from maternal blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy-Weinberg Equilibrium (HWE) for genotype frequencies was assessed, using the Chi-Square test with p < 0.006 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database Phase III, using Chi-square or Fisher's exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.006 for statistical significance.
Our study involved 1059 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian, Native Hawaiian, and Pacific Islander ancestry. The Asian subgroups included Japanese, Filipino, and Korean. The Pacific Islander subgroups included Marshallese and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p < 0.006) across all the population subgroups, with eight loci remaining for cross-subgroup comparisons. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino, 8/8 in Samoan, 6/8 in Native Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian, respectively. The percentage of cumulative risk alleles was 100% in both Japanese and Filipino, followed by 83.5% in Korean.
Compared to EUR, Asian subgroups, particularly Japanese, Filipino, and Korean, had the highest percentage of the cumulative uric acid risk alleles. These results could partly explain the increased risk of developing gout among some Asian ancestral subgroups compared to EUR.
痛风是一种炎症性疾病，其特征是尿酸单钠晶体（MSU）在远端关节内或周围沉淀。这是由慢性高尿酸血症（HU）——血液中尿酸水平升高引起的。尿酸转运蛋白的基因变异在决定人体内尿酸水平方面起着重要作用，使得一些种族和族裔群体或多或少更容易患高尿酸血症或痛风。本研究旨在使用生物样本库的DNA样本，估计亚洲、夏威夷原住民和太平洋岛民亚组中高尿酸血症和痛风风险等位基因的频率。
夏威夷大学的生物样本库提供了同意参与研究的产后妇女的DNA样本，这些妇女分别具有日本、菲律宾、韩国、夏威夷原住民、萨摩亚和马绍尔群岛血统。DNA先前已从母血中提取，并在癌症中心（檀香山，夏威夷）的基因组学和生物信息学共享资源中心进行基因分型。由于与高尿酸血症和痛风风险有显著关联，选择了九个尿酸基因：ABCG2、SLC2A9、SLC16A9、GCKR、SLC22A11、SLC22A12、LRR16A、PDZK1和SLC17A1。使用卡方检验评估基因型频率的哈迪-温伯格平衡（HWE），p < 0.006具有统计学意义。然后，在适当的情况下，使用卡方检验或费舍尔精确检验，将我们研究中的等位基因频率与千人基因组计划数据库第三阶段的欧洲人（EUR）进行比较。使用Bonferroni多重比较校正，p < 0.006具有统计学意义。
我们的研究涉及1059名18岁及以上的产后妇女，她们自我报告了各自的种族和族裔，包括亚洲、夏威夷原住民和太平洋岛民血统。亚洲亚组包括日本、菲律宾和韩国。太平洋岛民亚组包括马绍尔群岛和萨摩亚。所有研究参与者均无痛风病史。由于PDZK1基因在所有人群亚组中均偏离哈迪-温伯格平衡（p < 0.006），因此在最终分析中排除了该基因，剩下八个位点用于亚组间比较。与欧洲人相比，基因多态性频率存在显著差异——日本人中为8/8，韩国人中为6/8，菲律宾人中为6/8，萨摩亚人中为8/8，夏威夷原住民中为6/8，马绍尔群岛人中为6/8。日本人、菲律宾人、韩国人、萨摩亚人、马绍尔群岛人和夏威夷原住民的高尿酸血症和痛风风险等位基因指数分别为8、6、5、5、4和4。日本人和菲律宾人的累积风险等位基因百分比均为100%，其次是韩国人的83.5%。
与欧洲人相比，亚洲亚组，尤其是日本人、菲律宾人和韩国人，累积尿酸风险等位基因的百分比最高。这些结果可以部分解释某些亚洲祖先亚组与欧洲人相比痛风发病风险增加的原因。
