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

Details

• Personal Author:
  Abul-Husn NS ; Belbin GM ; Branch AD ; Friedman SL ; Kenny EE ; Ma N ; Pejaver V ; Rutledge SM ; Soper ER
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Fibrosis Genetics Occupational Health Race Factors Safety
• Keywords:
  Author Keywords: Biobank Electronic Health Records FIB-4 Score Genes Genetic Factors Genetic Risk Hispanic/Latino HSD17B13 Liver Disease Liver Fibrosis NAFLD PNPLA3 Racial Factors

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• ISSN:
  1542-3565
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  21
• Issue:
  10
• NIOSHTIC Number:
  nn:20068546
• Citation:
  Clin Gastroenterol Hepatol 2023 Sep; 21(10):2578-2587.e11
• Contact Point Address:
  Noura S. Abul-Husn, MD, PhD, The Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1041, New York, New York 10029
• Email:
  noura.abul-husn@mssm.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  Clinical Gastroenterology and Hepatology
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ba7a5ff7c2c7db2a5f4971fc6fc62152698da2c7f317db6cde444f466efdcd0aad99fc5cae99e3c1b0b0d74f08639c05e88c0737ba0ed19f15d49e8e44aab8c4
• Download URL:
  https://stacks.cdc.gov/view/cdc/207157/cdc_207157_DS1.pdf
• File Type:
  [PDF - 1.01 MB ]