TY - JOUR
T1 - Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children
AU - Larrieta-Carrasco, Elena
AU - León-Mimila, Paola
AU - Villarreal-Molina, Teresa
AU - Villamil-Ramírez, Hugo
AU - Romero-Hidalgo, Sandra
AU - Jacobo-Albavera, Leonor
AU - Gutiérrez-Vidal, Roxana
AU - López-Contreras, Blanca E.
AU - Guillén-Pineda, Luz E.
AU - Sánchez-Muñoz, Fausto
AU - Bojalil, Rafael
AU - Mejía-Domínguez, Ana M.
AU - Méndez-Sánchez, Nahúm
AU - Domínguez-López, Aaron
AU - Aguilar-Salinas, Carlos A.
AU - Canizales-Quinteros, Samuel
N1 - Funding Information:
We thank Salvador Ramírez-Jiménez for his technical assistance. This research was supported by grant 11386 from the Consejo Nacional de Ciencia y Tecnología (CONACyT).
PY - 2013/5/15
Y1 - 2013/5/15
N2 - 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 (>35U/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.
AB - 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 (>35U/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.
KW - Alanine transaminases
KW - I148M/PNPLA3
KW - Mexican children
KW - NAFLD
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=84876320981&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2013.03.038
DO - 10.1016/j.gene.2013.03.038
M3 - Artículo
SN - 0378-1119
VL - 520
SP - 185
EP - 188
JO - Gene
JF - Gene
IS - 2
ER -