PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study.
The secretory phospholipase A2II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.
Department of Human Genetics and Genomics, Instituto Nacional de Perinatología Isidro Espinoza de los Reyes, Mexico City, Mexico.
Irma Eloisa
IE
Monroy-Muñoz
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Javier
J
Angeles-Martinez
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Rosalinda
R
Posadas-Sánchez
Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Teresa
T
Villarreal-Molina
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Edith
E
Alvarez-León
CICSA, Universidad Anahuac, Mexico.
Carmina
C
Flores-Dominguez
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Guillermo
G
Cardoso-Saldaña
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Aida
A
Medina-Urrutia
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Juan Gabriel
JG
Juárez-Rojas
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Carlos
C
Posadas-Romero
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gvargas63@yahoo.com.
Gilberto Vargas
GV
Alarcon
D050197:Atherosclerosis / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054501:Group II Phospholipases A2 / Q000235:genetics*; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D015810:Linkage Disequilibrium; D050155:Lipogenesis; D008066:Lipolysis; D024821:Metabolic Syndrome / Q000235:genetics*; D008800:Mexico; D020641:Polymorphism, Single Nucleotide
D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human
Metabolic syndrome; Polymorphisms; Secretory phospholipase A(2) II A; Subclinical atherosclerosis; Type 2 diabetes mellitus