Peroxisome proliferator-activated receptor gamma-2 P12A polymorphism and risk of acute myocardial infarction, coronary heart disease and ischemic stroke: a case-cohort study and meta-analyses.
BACKGROUND
The alanine allele of P12A polymorphism in PPARG gene in a few studies has been associated with a reduced or increased risk of acute myocardial infarction (AMI). Yet, the risk relation has not been confirmed, and data on ischemic stroke (IS) is scarce. We therefore investigated the role of this polymorphism on occurrence of AMI, coronary heart disease (CHD) and IS.


RESULTS
We performed a case-cohort study in 15,236 initially healthy Dutch women and applied a Cox proportional hazards model to study the relation of the P12A polymorphism and AMI (n = 71), CHD (n = 211), and IS (n = 49) under different inheritance models. In addition, meta-analyses of published studies were performed. Under the dominant inheritance model, carriers of the alanine allele compared with those with the more common genotype were not at increased or decreased risk of CHD (hazard ratio [HR] = 0.82; 95% confidence interval [CI], 0.58 to 1.17) and of IS (HR = 1.03; 95% CI, 0.14 to 7.74). In addition no relations were found under the recessive and additive models. Our meta-analyses corroborated these findings by showing no significant association. For AMI we found a borderline significant association under dominant (HR = 0.49; 95% CI, 0.26 to 0.94), and additive (HR = 0.51; 95% CI, 0.26 to 1.00) models which could be due to chance, because of small cases in this subgroup. The meta-analysis did not show any association between the polymorphism and risk of AMI under the different genetic models.


CONCLUSIONS
Our study in healthy Dutch women in combination with the meta-analyses of previous reports does not provide support for a role of P12A polymorphism in PPARG gene in MI and CHD risk. Also our study shows that the polymorphism has no association with IS risk.
Zafarmand
Mohammad Hadi
MH
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Str 6.131, 3584 CX, Utrecht, The Netherlands.
van der Schouw
Yvonne T
YT
Grobbee
Diederick E
DE
de Leeuw
Peter W
PW
Bots
Michiel L
ML
D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009203:Myocardial Infarction / Q000235:genetics*; D009426:Netherlands; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*
D047495:PPAR gamma