Association of the I148M/PNPLA3 (rs738409) polymorphism with premature coronary artery disease, fatty liver, and insulin resistance in type 2 diabetic patients and healthy controls. The GEA study.
The aim of this study was to evaluate the potential use of the I148M/PNPLA3 (rs738409) gene polymorphism as a susceptibility marker for premature coronary artery disease (pCAD) and/or cardiovascular risk factors in Mexican type 2 diabetes mellitus patients (T2DM). The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 2572 subjects (1103 with pCAD and 1469 healthy controls) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed in all individuals. The association between the I148M/PNPLA3 (rs738409) gene polymorphism with pCAD and other metabolic and cardiovascular risk factors was evaluated using logistic regression analysis under different statistical approaches including dominant, recessive, heterozygous, additive, and co-dominant models. The polymorphism was not associated with pCAD in the whole group of participants, however, when patients and controls were divided into those with and without T2DM, under additive model, the polymorphism was associated with the presence of pCAD only in patients with T2DM (OR=1.20, 95% CI: 1.01-1.42, Padd=0.042). On the other hand, under several models adjusted for age, gender, body mass index and T2DM, the polymorphism was associated with increased risk of fatty liver and elevated levels of alanine transaminase (ALT) in the whole group of pCAD patients and controls. In the control group, the polymorphism was associated with insulin resistance and coronary artery calcification (CAC) score≥10 under several models. The results suggest that the I148M/PNPLA3 (rs738409) polymorphism is associated with the presence of pCAD in T2DM patients and with some cardiometabolic parameters. The association detected with CAC in the control group indicates that this polymorphism could be a marker for subclinical atherosclerosis.
Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: rossy_posadas_s@yahoo.it.
Rosalinda
R
Posadas-Sánchez
Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Ángel René
ÁR
López-Uribe
Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Carlos
C
Posadas-Romero
Molecular Biology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Nonanzit
N
Pérez-Hernández
Molecular Biology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
José Manuel
JM
Rodríguez-Pérez
Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Wendy Angélica
WA
Ocampo-Arcos
Molecular Biology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
José Manuel
JM
Fragoso
Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Guillermo
G
Cardoso-Saldaña
Molecular Biology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Gilberto
G
Vargas-Alarcón
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D002114:Calcinosis / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D005819:Genetic Markers; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
Adiponutrin; Coronary artery calcification; Fatty liver; I148M/PNPLA3 polymorphism; Insulin resistance; Type 2 diabetes mellitus