Short Communication Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children Elena Larrieta-Carrasco a , Paola León-Mimila b , Teresa Villarreal-Molina c , Hugo Villamil-Ramírez b , Sandra Romero-Hidalgo d , Leonor Jacobo-Albavera b , Roxana Gutiérrez-Vidal b , Blanca E. López-Contreras b , Luz E. Guillén-Pineda e , Fausto Sánchez-Muñoz f , Rafael Bojalil f , Ana M. Mejía-Domínguez g , Nahúm Méndez-Sánchez h , Aaron Domínguez-López i , Carlos A. Aguilar-Salinas e , Samuel Canizales-Quinteros a, b, ⁎ a Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Mexico City, Mexico b Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico c Laboratorio de Genómica de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico d Laboratorio de Genómica Computacional, INMEGEN, Mexico City, Mexico e Departamento de Endocrinología y Metabolismo, INCMNSZ, Mexico City, Mexico f Departamento de Inmunología, Instituto Nacional de Cardiología “Ignacio Chávez” (INCICh), Mexico City, Mexico g Banco de Sangre, INCICh, Mexico City, Mexico h Unidad de Investigación del Hígado, Fundación Médica Sur, Mexico City, Mexico i Departamento de Gastroenterología, INCMNSZ, Mexico City, Mexico abstract article info Article history: Accepted 8 March 2013 Available online 17 March 2013 Keywords: I148M/PNPLA3 Alanine transaminases Mexican children Obesity NAFLD Background and aims: Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly asso- ciated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to es- timate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children. Methods: A total of 1037 non-related Mexican children aged 6 to 12 years were genotyped for the I148M vari- ant. Anthropometric, clinical and metabolic parameters were collected from all participants. Results: Elevated ALT levels (>35 U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in nor- mal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR = 3.7, 95% CI 2.3–5.9; P = 3.7 × 10 -8 ), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P = 0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR = 19.9, 95% CI 2.5–157.7; P = 0.005) than overweight and obese children (OR = 3.4, 95% CI 1.3–8.9; P = 0.014 and OR = 3.1, 95% CI 1.7–5.5; P = 1.4 x10 -4 , respectively). Conclusions: The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The prevalence of obesity is increasing worldwide, particularly in children. In Mexico more than 25% of the children are overweight or obese (Olaiz-Fernández et al., 2006). Obesity is the main risk factor for nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in children (Carter-Kent et al., 2009). The preva- lence of hepatic steatosis in the pediatric population is estimated to be 10% and may be as high as 38% among obese children (Schwimmer et al., 2006), being a matter of concern because longitudinal studies of Gene 520 (2013) 185–188 Abbreviations: NAFLD, non-alcoholic fatty liver disease; ALT, alanine transaminase; AST, aspartate transaminases; PNPLA3, patatin-like phospholipase domain-contain 3; BMI, body mass index; HOMA-IR, homeostasis model assessment for insulin resistance; HDL-C, high-density lipoprotein cholesterol; OR, odds ratio. ⁎ Corresponding author at: Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Colonia Arenal Tepepan, Tlalpan 14610, D. F., México. Tel.: +52 55 53 50 19 00; fax: +52 55 53 50 19 99. E-mail address: cani@unam.mx (S. Canizales-Quinteros). 0378-1119/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.gene.2013.03.038 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene