title: Interactions between peroxisome proliferator-activated receptor-gamma 2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication.
abstract: OBJECTIVE
  The combination of small birth size and the Pro12Pro variant of the peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) 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-gamma 2 gene polymorphism, and whether the use of any class of antihypertensive medication is related to birth size.
  
  
  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-gamma 2 gene was determined using the polymerase chain reaction single-strand conformation polymorphism method.
  
  
  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 treatment 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.
authors.affiliation: National Public Health Institute, Helsinki, University of Helsinki, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Ylihärsilä
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Tom
authors.initials: T
authors.lastname: Forsén
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: David J P
authors.initials: DJ
authors.lastname: Barker
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001724:Birth Weight / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D001827:Body Height / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D047495:PPAR gamma