TY - JOUR
T1 - Effect of the ppar gamma2 pro12ala polymorphism on the risk of myocardial infarction
AU - Vos, Hans L.
AU - Doggen, Carine J.M.
AU - Rosendaal, Frits R.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - PPAR (Peroxisome Proliferator Activated Receptor) gamma is a nuclear receptor that plays an important role in the differentiation of fibroblasts to adipose cells and in lipid metabolism. A polymorphism, Prol2Ala, has been described in the gamma2 form of the mRNA, which is transcribed from an alternative promoter, that is mainly active in adipocytes. It has been reported that the AIal2-form of PPARgamma2 is a weaker transactivator than the wildtype form. On the physiological level many apparently conflicting data have been reported. It has been claimed that Ala-carriers (hétérozygotes and/or homozygotes) have a higher Body Mass Index (BMI) and altered lipid parameters (e.g. increased cholesterol), but most of the results are inconsistent. We have assessed the effect of the Pro 12Ala polymorphism on the risk of myocardial infarction in a large case-control study, the Study of Myocardial Infarctions Leiden (SMILE). This study consists of 560 men with a first myocardal infarction before the age of 70 and 646 healthy controls. The allelic frequency of Alal2 was 13.1% in cases and 11.3% in controls. The distribution of the genotypes is shown in the table. While the risk was not increased in heterozygous Ala-carriers, homozygotes had a two-fold increased risk of myocardial infarction (OR=2.0. CI95 = 1.0-4.2). In both cases and controls, we do not find any evidence for an effect of the heterozygous genotype on BMI, diabetes, triglycérides, total cholesterol, HDL-cholesterol. or PAI-1 levels, variables that have all been reported to be affected in hétérozygotes. In Ala/Ala homozygotes mean BMI and total cholesterol were increased relative to the other genotypes, but confidence intervals were wide. Our data suggest that only the Ala/Ala homozygotes of the PPAR gamma2 Prol2Ala polymorphism are at increased risk of myocardial infarction. In addition, the homozygous genotype may affect a number of traditional risk factors of MI, but a very large study population will be required to accurately assess the effect of this genotype on a number of relevant biochemical variables. Table. Distribution of the genotypes among cases and controls. cases controls (%) total (%) Pro/Pro 434(77.5) 512(79.3) 946(78.4) Pro/Ala 105(18.8) 122(18.9) 227(18.8) Ala/Ala 21(3.8) 12(1.9) 33(2.7) total 560(100.) 646(100.) 1206(100.).
AB - PPAR (Peroxisome Proliferator Activated Receptor) gamma is a nuclear receptor that plays an important role in the differentiation of fibroblasts to adipose cells and in lipid metabolism. A polymorphism, Prol2Ala, has been described in the gamma2 form of the mRNA, which is transcribed from an alternative promoter, that is mainly active in adipocytes. It has been reported that the AIal2-form of PPARgamma2 is a weaker transactivator than the wildtype form. On the physiological level many apparently conflicting data have been reported. It has been claimed that Ala-carriers (hétérozygotes and/or homozygotes) have a higher Body Mass Index (BMI) and altered lipid parameters (e.g. increased cholesterol), but most of the results are inconsistent. We have assessed the effect of the Pro 12Ala polymorphism on the risk of myocardial infarction in a large case-control study, the Study of Myocardial Infarctions Leiden (SMILE). This study consists of 560 men with a first myocardal infarction before the age of 70 and 646 healthy controls. The allelic frequency of Alal2 was 13.1% in cases and 11.3% in controls. The distribution of the genotypes is shown in the table. While the risk was not increased in heterozygous Ala-carriers, homozygotes had a two-fold increased risk of myocardial infarction (OR=2.0. CI95 = 1.0-4.2). In both cases and controls, we do not find any evidence for an effect of the heterozygous genotype on BMI, diabetes, triglycérides, total cholesterol, HDL-cholesterol. or PAI-1 levels, variables that have all been reported to be affected in hétérozygotes. In Ala/Ala homozygotes mean BMI and total cholesterol were increased relative to the other genotypes, but confidence intervals were wide. Our data suggest that only the Ala/Ala homozygotes of the PPAR gamma2 Prol2Ala polymorphism are at increased risk of myocardial infarction. In addition, the homozygous genotype may affect a number of traditional risk factors of MI, but a very large study population will be required to accurately assess the effect of this genotype on a number of relevant biochemical variables. Table. Distribution of the genotypes among cases and controls. cases controls (%) total (%) Pro/Pro 434(77.5) 512(79.3) 946(78.4) Pro/Ala 105(18.8) 122(18.9) 227(18.8) Ala/Ala 21(3.8) 12(1.9) 33(2.7) total 560(100.) 646(100.) 1206(100.).
UR - https://www.scopus.com/pages/publications/33748561174
M3 - Article
AN - SCOPUS:33748561174
SN - 0006-4971
VL - 96
SP - 62b
JO - Blood
JF - Blood
IS - 11 PART II
ER -