Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries

医学 全基因组关联研究 基因分型 遗传谱系 肝病 内科学 生命银行 遗传关联 基因型 人口学 单核苷酸多态性 遗传学 生物 基因 环境卫生 人口 社会学
作者
Stephanie M. Rutledge,Emily R. Soper,Ning Ma,Vikas Pejaver,Scott L. Friedman,Andrea D. Branch,Eimear E. Kenny,Gillian M. Belbin,Noura S. Abul‐Husn
出处
期刊:Clinical Gastroenterology and Hepatology [Elsevier BV]
卷期号:21 (10): 2578-2587.e11 被引量:9
标识
DOI:10.1016/j.cgh.2022.12.025
摘要

Background & Aims Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease–associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record–linked biobank in New York City. Methods This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. Results Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). Conclusions Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals. Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease–associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record–linked biobank in New York City. This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
科研助手6应助gz采纳,获得10
1秒前
彭于晏应助gz采纳,获得10
1秒前
鱼与木头发布了新的文献求助10
2秒前
绿泡泡发布了新的文献求助10
3秒前
今后应助Transition采纳,获得10
5秒前
Chelry发布了新的文献求助10
5秒前
大大怪发布了新的文献求助10
6秒前
乐乐应助lina采纳,获得10
8秒前
9秒前
9秒前
gz完成签到,获得积分10
12秒前
哲别发布了新的文献求助10
13秒前
SciGPT应助科研通管家采纳,获得10
16秒前
香蕉觅云应助科研通管家采纳,获得10
16秒前
16秒前
充电宝应助科研通管家采纳,获得10
16秒前
李健应助科研通管家采纳,获得10
16秒前
义气严青完成签到,获得积分10
16秒前
17秒前
17秒前
18秒前
22秒前
某某完成签到,获得积分20
24秒前
25秒前
Owen应助shore采纳,获得10
25秒前
小熊完成签到,获得积分10
26秒前
英姑应助丸子_2025000采纳,获得10
27秒前
yydragen应助rita_sun1969采纳,获得30
27秒前
可爱的函函应助大喵采纳,获得10
28秒前
32秒前
包李发布了新的文献求助10
32秒前
33秒前
打打应助自由的读书人采纳,获得10
37秒前
共享精神应助bbh采纳,获得10
38秒前
研友_VZG7GZ应助bbh采纳,获得10
38秒前
小小完成签到,获得积分10
38秒前
大喵发布了新的文献求助10
38秒前
漫奏曲发布了新的文献求助10
39秒前
42秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989797
求助须知:如何正确求助?哪些是违规求助? 3531914
关于积分的说明 11255516
捐赠科研通 3270597
什么是DOI,文献DOI怎么找? 1805008
邀请新用户注册赠送积分活动 882181
科研通“疑难数据库(出版商)”最低求助积分说明 809190