RESUMO
The aim of the present study was to evaluate the role of the C-514T (rs1800588) gene polymorphism of the hepatic lipase (LIPC) as susceptibility marker for fatty liver in the Mexican population. The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 1468 subjects (980 with and 488 without fatty liver) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed on all individuals. The polymorphism was not associated with fatty liver, however, under dominant model, the TT genotype was associated with increased levels of triglycerides (P=0.0002), apolipoprotein A1 (P=0.015), triglycerides/HDL-cholesterol index (P=0.046) and increased frequency of type 2 diabetes mellitus (P=0.045). On the other hand, the same genotype was associated with the presence of small LDLs (P=0.003). The risk analysis showed that under a dominant model, the LIPC C-514T polymorphism was associated with increased risk of type 2 diabetes (OR=1.42, P=0.029), hypertriglyceridemia (OR=1.36, P=0.006), and coronary artery calcification (CAC)≥1 (OR=1.44, P=0.015) and decreased risk of hypoalphalipoproteinemia (OR=0.78, P=0.036). The results suggest that the LIPC C-154T polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population. The association detected with CAC indicates that this polymorphism could be a marker for subclinical atherosclerosis.
Assuntos
Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Fígado Gorduroso/genética , Lipase/genética , Polimorfismo Genético/genética , Adulto , Idoso , Apolipoproteína A-I/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Seguimentos , Humanos , Lipoproteínas HDL/metabolismo , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Triglicerídeos/metabolismoRESUMO
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.
Assuntos
Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Fígado Gorduroso/genética , Resistência à Insulina/genética , Lipase/genética , Proteínas de Membrana/genética , Adulto , Alanina Transaminase/sangue , Calcinose/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
The CLEC16A gene has an important role in the immune activation and regulation inflammatory. This gene encodes to C-type lectin domain that is involved in the recognition of DAMPS. The aim of this study was assess the CLEC16A gene polymorphisms in the risk of developing ACS in a group of patients. Four rs12708716, rs12917716, rs6498142 and rs9925481 (positions 146529 A>G, 155804 G>C, 47905 C>G and 64135 C>T, respectively) single nucleotide polymorphisms of CLEC16A gene were analyzed by TaqMan assays in a group of 452 patients with ACS and 456 healthy controls. The analysis was performed on the total group of individuals and then in groups of men and women separately. Under co-dominant model adjusted by cardiovascular risk factors the rs12708716 (146529 A>G) and rs12917716 (155804 G>C) polymorphisms were significantly associated with decrease risk of ACS in men (OR=0.16, PCo-dom=0.027 and OR=0.37, PCo-dom=0.016, respectively). In summary, our data suggests that two polymorphisms of the CLEC16A gene play an important role in the developing of ACS in men.
Assuntos
Síndrome Coronariana Aguda/genética , Lectinas Tipo C/genética , Modelos Genéticos , Proteínas de Transporte de Monossacarídeos/genética , Polimorfismo Genético , Caracteres Sexuais , Síndrome Coronariana Aguda/etnologia , Síndrome Coronariana Aguda/imunologia , Idoso , Feminino , Humanos , Lectinas Tipo C/imunologia , Masculino , México , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos/imunologia , Fatores de RiscoRESUMO
Epidemiological and clinical studies have shown that a low plasma highdensity lipoprotein cholesterol (HDL-C) level is a strong predictor of cardiovascular disease (CVD). Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the formation, maturation and function of HDL. Therefore impaired LCAT function may enhance atherosclerosis because of defective cholesterol transport. In this study, we examined a 34-year old LCATdeficient patient and eight first-degree family members. There was a strong family history for CVD and type 2 diabetes mellitus (DM2). The proband was found homozygous for a previously reported LCAT gene mutation (Thr37Met). A sister and two sons of the proband were heterozygous for the same mutation. The proband had DM2 and showed severe multivessel coronary artery disease, corneal opacification and extremely low HDL-C levels. Large HDL particles were absent while small HDL particles were increased. The HDL of the patient had a reduced ability to promote cell cholesterol efflux, and the lowdensity lipoproteins (LDL) were more susceptible to oxidation. Among his family members, two heterozygotes and one non-carrier had early carotid or coronary atherosclerosis. In conclusion, as the increased LDL oxidability and structural and functional abnormalities of HDL particles have been reported in patients with obesity and diabetes, the results suggested that the adverse coronary risk profile, and not being LCAT deficient, may be responsible for the CVD found in our proband, and for the early atherosclerosis observed in the two heterozygotes and in the wildtype family members.