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A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity.
Exp Mol Pathol 2015; 98(2):178-83EM

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.

Authors+Show Affiliations

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.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.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.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.Laboratorio de Enfermedades Cardiovasculares y Óseas, INMEGEN, México City 14610, Mexico.Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), México City 14000, 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.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.Clínica de Obesidad, Hospital Rubén Leñero, México City 11340, Mexico.Unidad de Investigación de Hígado, Fundación Médica Sur, México City 14050, Mexico.Departamento de Fisiología de la Nutrición, INCMNSZ, México City 14000, Mexico.Departamento de Patología Experimental, INCMNSZ, México City 14000, Mexico.Laboratorio de Enfermedades Cardiovasculares y Óseas, INMEGEN, México City 14610, Mexico.Clínica de Obesidad, Hospital Rubén Leñero, México City 11340, Mexico.Departamento de Endocrinología y Metabolismo, INCMNSZ, México City 14000, 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. Electronic address: cani@unam.mx.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25597287

Citation

León-Mimila, Paola, et al. "A Genetic Risk Score Is Associated With Hepatic Triglyceride Content and Non-alcoholic Steatohepatitis in Mexicans With Morbid Obesity." Experimental and Molecular Pathology, vol. 98, no. 2, 2015, pp. 178-83.
León-Mimila P, Vega-Badillo J, Gutiérrez-Vidal R, et al. A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity. Exp Mol Pathol. 2015;98(2):178-83.
León-Mimila, P., Vega-Badillo, J., Gutiérrez-Vidal, R., Villamil-Ramírez, H., Villareal-Molina, T., Larrieta-Carrasco, E., ... Canizales-Quinteros, S. (2015). A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity. Experimental and Molecular Pathology, 98(2), pp. 178-83. doi:10.1016/j.yexmp.2015.01.012.
León-Mimila P, et al. A Genetic Risk Score Is Associated With Hepatic Triglyceride Content and Non-alcoholic Steatohepatitis in Mexicans With Morbid Obesity. Exp Mol Pathol. 2015;98(2):178-83. PubMed PMID: 25597287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity. AU - León-Mimila,Paola, AU - Vega-Badillo,Joel, AU - Gutiérrez-Vidal,Roxana, AU - Villamil-Ramírez,Hugo, AU - Villareal-Molina,Teresa, AU - Larrieta-Carrasco,Elena, AU - López-Contreras,Blanca E, AU - Kauffer,Luis R Macías, AU - Maldonado-Pintado,Diana G, AU - Méndez-Sánchez,Nahúm, AU - Tovar,Armando R, AU - Hernández-Pando,Rogelio, AU - Velázquez-Cruz,Rafael, AU - Campos-Pérez,Francisco, AU - Aguilar-Salinas,Carlos A, AU - Canizales-Quinteros,Samuel, Y1 - 2015/01/15/ PY - 2014/08/26/received PY - 2015/01/13/revised PY - 2015/01/14/accepted PY - 2015/1/20/entrez PY - 2015/1/20/pubmed PY - 2015/6/16/medline KW - GRS KW - Liver fat content KW - NAFLD KW - NASH KW - Polymorphisms SP - 178 EP - 83 JF - Experimental and molecular pathology JO - Exp. Mol. Pathol. VL - 98 IS - 2 N2 - 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. SN - 1096-0945 UR - https://www.unboundmedicine.com/medline/citation/25597287/A_genetic_risk_score_is_associated_with_hepatic_triglyceride_content_and_non_alcoholic_steatohepatitis_in_Mexicans_with_morbid_obesity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4800(15)00014-3 DB - PRIME DP - Unbound Medicine ER -