Abstract | BACKGROUND & AIMS: Little data are available from genome-wide association studies (GWASs) of liver histology in patients with nonalcoholic fatty liver disease ( NAFLD). We conducted a pilot GWAS in patients with NAFLD, characterized by histology, who were enrolled in the NASH Clinical Research Network (CRN) Database Study. METHODS: We studied clinical, laboratory, and histologic data from 236 non-Hispanic white women with NAFLD. We analyzed 324,623 single nucleotide polymorphisms (SNPs) from the 22 autosomal chromosomes. Multivariate-adjusted logistic regression analyses were conducted for binary outcomes, and linear regression analysis was applied for quantitative traits. A P value < 1 × 10(-6) was considered to be significant. RESULTS: In multivariate models adjusted for age, body mass index, diabetes, waist/hip ratios, and levels of glycated hemoglobin, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (P = 6.8 × 10(-7)). The degree of fibrosis was associated with the SNP rs343062 on chromosome 7 (P = 2.7 × 10(-8)). SNPs associated with lobular inflammation included SNP rs1227756 on chromosome 10 in COL13A1 (P = 2.0 × 10(-7)), rs6591182 on chromosome 11 (P = 8.6 × 10(-7)), and rs887304 on chromosome 12 in EFCAB4B (P = 7.7 × 10(-7)). SNPs associated with serum levels of alanine aminotransferase included rs2499604 on chromosome 1 (P = 2.2 × 10(-6)), rs6487679 on chromosome 12 in PZP (P = 1.3 × 10(-6)), rs1421201 on chromosome 18 (P = 1.0 × 10(-5)), and rs2710833 on chromosome 4 (P = 6.3 × 10(-7)). No significant associations were observed between genotypes and steatosis, ballooning degeneration, portal inflammation, or other features of NAFLD. CONCLUSIONS: A GWAS significantly associated genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts.
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Authors | Naga Chalasani, Xiuqing Guo, Rohit Loomba, Mark O Goodarzi, Talin Haritunians, Soonil Kwon, Jinrui Cui, Kent D Taylor, Laura Wilson, Oscar W Cummings, Yii-Der Ida Chen, Jerome I Rotter, Nonalcoholic Steatohepatitis Clinical Research Network |
Journal | Gastroenterology
(Gastroenterology)
Vol. 139
Issue 5
Pg. 1567-76, 1576.e1-6
(Nov 2010)
ISSN: 1528-0012 [Electronic] United States |
PMID | 20708005
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- DNA
- Farnesyl-Diphosphate Farnesyltransferase
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Topics |
- DNA
(genetics)
- Disease Progression
- Farnesyl-Diphosphate Farnesyltransferase
(genetics, metabolism)
- Fatty Liver
(genetics, metabolism, pathology)
- Female
- Follow-Up Studies
- Genetic Predisposition to Disease
- Genome-Wide Association Study
(methods)
- Genotype
- Humans
- Liver
(metabolism, pathology)
- Male
- Middle Aged
- Pilot Projects
- Polymorphism, Single Nucleotide
- Prognosis
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