Interactions between peroxisome proliferator-activated receptor-gamma 2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication
Ylihärsilä, H.; Eriksson, J.G.; Forsén, T.; Laakso, M.; Uusitupa, M.; Osmond, C.; Barker, D.J.P.
Journal of Hypertension 22(7): 1283-1287
2004
ISSN/ISBN: 0263-6352 PMID: 15201543 Document Number: 583127
Objective The combination of small birth size and the Pro12Pro variant of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene has been shown to be associated with insulin resistance, which is linked to hypertension. We examined whether the association between small body size at birth and adult blood pressure is modulated by PPAR-gamma2 gene polymorphism, and whether the use of any class of antihypertensive medication is related to birth size. Design and methods A total of 500 subjects from an original epidemiological cohort of 7086 men and women aged 65-75 years attended a clinical study. Two hundred and eight of them (73 men and 135 women) were taking antihypertensive medication and are included in this study. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined using the polymerase chain reaction single-strand conformation polymorphism method. Results and conclusions Hypertensive subjects with low birth weight or short length at birth and the Pro12Pro variant had raised systolic blood pressure. We suggest that insulin resistance enhances the regulatory responses of the renin-angiotensin system, leading to raised blood pressure levels. Those hypertensive subjects who had small birth size and the Pro12Pro variant tended to use angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB). This could be because insulin resistance interacts with the renin-angiotensin system in ways that make ACEI/ARB an effective therapy. Alternative explanations include more severe and teatment resistant hypertension, leading to application of ACEI/ARB, or co-morbid conditions, such as myocardial infarction and type 2 diabetes, known to be linked to low birth weight. (C) 2004 Lippincott Williams & Wilkins.