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Exp Mol Pathol. 2015 Apr;98(2):178-83. doi: 10.1016/j.yexmp.2015.01.012. Epub 2015 Jan 15.

A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity.

Author information

1
Programa de Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico; Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Instituto Nacional de Medicina Genómica (INMEGEN), México City 14610, Mexico.
2
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Instituto Nacional de Medicina Genómica (INMEGEN), México City 14610, Mexico.
3
Laboratorio de Enfermedades Cardiovasculares y Óseas, INMEGEN, México City 14610, Mexico.
4
Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), México City 14000, Mexico.
5
Clínica de Obesidad, Hospital Rubén Leñero, México City 11340, Mexico.
6
Unidad de Investigación de Hígado, Fundación Médica Sur, México City 14050, Mexico.
7
Departamento de Fisiología de la Nutrición, INCMNSZ, México City 14000, Mexico.
8
Departamento de Patología Experimental, INCMNSZ, México City 14000, Mexico.
9
Departamento de Endocrinología y Metabolismo, INCMNSZ, México City 14000, Mexico.
10
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Instituto Nacional de Medicina Genómica (INMEGEN), México City 14610, Mexico. Electronic address: cani@unam.mx.

Abstract

BACKGROUND AND AIMS:

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in individuals of European ancestry. The aim of the study was to test whether these genetic variants and a genetic risk score (GRS) are associated with elevated liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with morbid obesity.

METHODS:

130 morbidly obese Mexican individuals were genotyped for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly in liver biopsies and NASH was diagnosed by histology. A GRS was tested for association with liver fat content and NASH using logistic regression models. In addition, 95 ancestry-informative markers were genotyped to estimate population admixture proportions.

RESULTS:

After adjusting for age, sex and admixture, PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG content (P < 0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P = 0.086 for PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P = 1.0 × 10(-4) and 0.048, respectively), steatosis stage (P = 0.029), and higher ALT levels (P = 0.002). Subjects with GRS ≥ 6 showed a significantly increased risk of NASH (OR = 2.55, P = 0.045) compared to those with GRS ≤ 5. However, the GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P = 0.219).

CONCLUSION:

NAFLD associated loci in Europeans and a GRS based on these loci contribute to the accumulation of hepatic lipids and NASH in morbidly obese Mexican individuals.

KEYWORDS:

GRS; Liver fat content; NAFLD; NASH; Polymorphisms

PMID:
25597287
DOI:
10.1016/j.yexmp.2015.01.012
[Indexed for MEDLINE]

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