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Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children
Authors:Elena Larrieta-Carrasco,Paola Leó  n-Mimila,Teresa Villarreal-Molina,Hugo Villamil-Ramí  rez,Sandra Romero-Hidalgo,Leonor Jacobo-Albavera,Roxana Gutié  rrez-Vidal,Blanca E. Ló  pez-Contreras,Luz E. Guillé  n-Pineda,Fausto Sá  nchez-Muñ  oz,Rafael Bojalil,Ana M. Mejí  a-Domí  nguez,Nahú  m Mé  ndez-Sá  nchez,Aaron Domí  nguez-Ló  pez,Carlos A. Aguilar-Salinas,Samuel Canizales-Quinteros
Affiliation:1. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Mexico City, Mexico;2. Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico;3. Laboratorio de Genómica de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico;4. Laboratorio de Genómica Computacional, INMEGEN, Mexico City, Mexico;5. Departamento de Endocrinología y Metabolismo, INCMNSZ, Mexico City, Mexico;6. 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:

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 associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate 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 variant. 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 normal 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.
Keywords: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
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