Gastroenterology. 2010 Nov;139(5):1567-76, 1576.e1-6. doi: 10.1053/j.gastro.2010.07.057. Epub 2010 Aug 11.

Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.

Chalasani N, Guo X, Loomba R, Goodarzi MO, Haritunians T, Kwon S, Cui J, Taylor KD, Wilson L, Cummings OW, Chen YD, Rotter JI; Nonalcoholic Steatohepatitis Clinical Research Network.

Source

Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. nchalasa@iupui.edu

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.

Comment in

Polymorphism in the farnesyl diphosphate farnesyl transferase 1 gene and nonalcoholic fatty liver disease severity. [Gastroenterology. 2011]
Polymorphism in the farnesyl diphosphate farnesyl transferase 1 gene and nonalcoholic fatty liver disease severity.Ballestri S, Day CP, Daly AK. Gastroenterology. 2011 May; 140(5):1694-5. Epub 2011 Mar 24.

PMID:: 20708005; [PubMed - indexed for MEDLINE]
PMCID:: PMC2967576

Free PMC Article

Images from this publication.See all images (2)Free text

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials

anti-Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1) (C-Term) antibody - antibodies-online

Miscellaneous

See the articles recommended by F1000Prime's Faculty of 5,000 renowned researchers and clinicians, assisted by 5,000 associates. - F1000

Supplemental Content

Save items

PubReader: A whole new way to read scientific literature at PubMed Central.

Related citations in PubMed

The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. [Hepatology. 2010]
The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease.
Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ, NASH CRN. Hepatology. 2010 Sep; 52(3):894-903.
Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. [PLoS One. 2012]
Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese.
Kawaguchi T, Sumida Y, Umemura A, Matsuo K, Takahashi M, Takamura T, Yasui K, Saibara T, Hashimoto E, Kawanaka M, et al. PLoS One. 2012; 7(6):e38322. Epub 2012 Jun 14.
Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. [PLoS Genet. 2011]
Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.
Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Launer LJ, et al. PLoS Genet. 2011 Mar; 7(3):e1001324. Epub 2011 Mar 10.
Review Update on nonalcoholic fatty liver disease: genes involved in nonalcoholic fatty liver disease and associated inflammation. [Curr Opin Clin Nutr Metab Care...]
Review Update on nonalcoholic fatty liver disease: genes involved in nonalcoholic fatty liver disease and associated inflammation.
Tilg H, Moschen A. Curr Opin Clin Nutr Metab Care. 2010 Jul; 13(4):391-6.
Review The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. [Clin Liver Dis. 2004]
Review The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease.
McCullough AJ. Clin Liver Dis. 2004 Aug; 8(3):521-33, viii.

See reviews... See all...

Cited by 8 PubMed Central articles

Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease. [World J Gastroenterol. 2012]
Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease.
Li YY. World J Gastroenterol. 2012 Dec 7; 18(45):6546-51.
Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population. [PLoS One. 2012]
Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population.
Peng XE, Wu YL, Lin SW, Lu QQ, Hu ZJ, Lin X. PLoS One. 2012; 7(11):e50256. Epub 2012 Nov 30.
Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population. [BMC Med Genet. 2012]
Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population.
Li Y, Xing C, Tian Z, Ku HC. BMC Med Genet. 2012 Nov 23; 13:113. Epub 2012 Nov 23.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
Gene (nucleotide/PMC)
Records in Gene identified from shared sequence and PMC links.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
MedGen
Related information in MedGen
Nucleotide
Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
References for this PMC Article
Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
SNP (Cited)
Nucleotide polymorphism records from dbSNP that have NCBI dbSNP identifiers reported in the PubMed abstract of the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
SNP
Nucleotide polymorphism records from dbSNP that have current articles as submitter-provided references.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Free in PMC
Free full text articles in PMC
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Genome-wide association study identifies variants associated with histologic fea...
Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
Gastroenterology. 2010 Nov ;139(5):1567-76, 1576.e1-6. doi: 10.1053/j.gastro.2010.07.057. Epub 2010 Aug 11 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: