A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity

Objective: Peroxisome proliferator-activated receptor-gamma2 (PPAR gamma2) is an important regulator of adipose tissue metabolism and insulin sensitiv ity The aim of this investigation was to determine whether a PPAR gamma2 Pr o12Ala polymorphism was associated with cardiovascular risk factors (obesit y, blood pressure, diabetes and blood lipids) in Western Australian Caucasi ans (n = 663). Design: Subjects were selected from two population studies (the Carotid Ult rasound Disease Assessment Study (CUDAS) and Busselton Population Health Su rvey) on the basis of body mass index (BMI). 292 obese (BMI greater than or equal to 30 kg/m(2)) and 371 lean (BMI <25 kg/m(2)) subjects were studied. Methods: Blood pressure and anthropometric measurements were collected from all participants, as well as a fasting venous blood sample. Biochemical me asurements thigh-density lipoprotein (HDL)and low-density lipoprotein-chole sterol, triglycerides) and PPAR<gamma>2 Pro12Ala genotype were also determi ned. Results: Obese Pro/Ala and Ala/Ala subjects had lower levels of HDL-cholest erol (P = 0.032) and a trend towards higher levels of triglycerides (P = 0. 055) compared with obese Pro/Pro subjects. In the obese group, the Ala alle le was significantly associated with the presence of combined hyperlipidaem ia (odds ratio = 2.33, P = 0.042). There was no significant difference in t he frequency of the polymorphism between lean and obese groups (P = 0.069). No association was observed between Pro12Ala genotype and obesity, blood p ressure or diabetes in either group, Conclusions: Obese carriers of the Pro12Ala polymorphism have a greater ris k of developing combined hyperlipidaemia, possibly due to impaired activati on of PEAR gamma target genes. The Pro12Ala polymorphism is not directly as sociated with obesity, hypertension or diabetes in this population.