Division of Hepatology, Loyola University Medical Center, Maywood, Illinois.
Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois.
Clin Gastroenterol Hepatol. 2019 Oct;17(11):2301-2309. doi: 10.1016/j.cgh.2019.02.007. Epub 2019 Feb 8.
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of these disparities.
We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data from the Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively.
Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio [OR], 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry had a positive association with level of ALT (r = 6.61%; P < .001), whereas African (r = -3.84%; P < .001) and European (r = -4.31%; P < .001) ancestry were inversely associated with level of ALT.
American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.
非酒精性脂肪性肝病（NAFLD）在西班牙裔/拉丁裔人群中不成比例地高发。然而，西班牙裔/拉丁裔各民族之间的高发程度存在差异。我们旨在研究这些差异的机制。
我们使用美国西班牙裔/拉丁裔成年人的基于人群的西班牙裔社区健康研究/拉丁裔研究的数据，检查了与 NAFLD 相关的遗传变异和大陆血统与疑似 NAFLD、丙氨酸氨基转移酶（ALT）水平和肝纤维化之间的关联。我们评估了来自 2008 年至 2011 年四个城市的 16415 名西班牙裔/拉丁裔成年人的数据。根据氨基转移酶水平和 FIB-4 评分的不明原因升高，分别确定疑似 NAFLD 或肝纤维化的患者。
在有可用遗传和氨基转移酶数据的 9342 名参与者中，PNPLA3 G 等位基因（比值比[OR]，1.53；95%CI，1.41-1.66）、TM6SF2 T 等位基因（OR，1.41；95%CI，1.20-1.67）和 PPP1R3B G 等位基因（OR，1.16；95%CI，1.06-1.28）与疑似 NAFLD 相关。PNPLA3 G 还与 ALT 水平升高有关，除了在具有多米尼加和南美背景的参与者中，以及与肝纤维化有关。PNPLA3 G 在西班牙裔/拉丁裔人群中的频率较高（41%），TM6SF2 T 较低（5%）。PNPLA3 G 的频率在西班牙裔背景群体中存在差异，其中墨西哥裔最高（52%），多米尼加裔最低（23%）。在调整人口统计学、临床和行为因素以及 PNPLA3 G、TM6SF2 T 和 PPP1R3B G 后，美洲血统与 ALT 水平呈正相关（r=6.61%；P<.001），而非洲血统（r=-3.84%；P<.001）和欧洲血统（r=-4.31%；P<.001）与 ALT 水平呈负相关。
美洲血统和 PNPLA3 G 是美国西班牙裔/拉丁裔人群 ALT 水平的独立预测因子，可能部分解释了美国西班牙裔/拉丁裔人群中 NAFLD 的差异。
