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Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity.
Hum Hered 2013; 75(1):34-43HH

Abstract

OBJECTIVE

Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity.

METHODS

In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed.

RESULTS

We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD.

CONCLUSION

NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.

Authors+Show Affiliations

Division of Gastroenterology, University of Maryland School of Medicine, Baltimore, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23594525

Citation

Gorden, Alexis, et al. "Genetic Variation at NCAN Locus Is Associated With Inflammation and Fibrosis in Non-alcoholic Fatty Liver Disease in Morbid Obesity." Human Heredity, vol. 75, no. 1, 2013, pp. 34-43.
Gorden A, Yang R, Yerges-Armstrong LM, et al. Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity. Hum Hered. 2013;75(1):34-43.
Gorden, A., Yang, R., Yerges-Armstrong, L. M., Ryan, K. A., Speliotes, E., Borecki, I. B., ... Gerhard, G. S. (2013). Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity. Human Heredity, 75(1), pp. 34-43. doi:10.1159/000346195.
Gorden A, et al. Genetic Variation at NCAN Locus Is Associated With Inflammation and Fibrosis in Non-alcoholic Fatty Liver Disease in Morbid Obesity. Hum Hered. 2013;75(1):34-43. PubMed PMID: 23594525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity. AU - Gorden,Alexis, AU - Yang,Rongze, AU - Yerges-Armstrong,Laura M, AU - Ryan,Kathleen A, AU - Speliotes,Elizabeth, AU - Borecki,Ingrid B, AU - Harris,Tamara B, AU - Chu,Xin, AU - Wood,G Craig, AU - Still,Christopher D, AU - Shuldiner,Alan R, AU - Gerhard,Glenn S, AU - ,, Y1 - 2013/04/10/ PY - 2012/08/21/received PY - 2012/11/27/accepted PY - 2013/4/19/entrez PY - 2013/4/19/pubmed PY - 2013/12/18/medline SP - 34 EP - 43 JF - Human heredity JO - Hum. Hered. VL - 75 IS - 1 N2 - OBJECTIVE: Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. METHODS: In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. RESULTS: We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. CONCLUSION: NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis. SN - 1423-0062 UR - https://www.unboundmedicine.com/medline/citation/23594525/Genetic_variation_at_NCAN_locus_is_associated_with_inflammation_and_fibrosis_in_non_alcoholic_fatty_liver_disease_in_morbid_obesity_ L2 - https://www.karger.com?DOI=10.1159/000346195 DB - PRIME DP - Unbound Medicine ER -