PRESENCE OF THE ALA ALLELE IN THE PPAR-GAMMA GENE IS NOT PROTECTIVE AGAINST RISK OF IMPAIRED GLUCOSE METABOLISM ASSOCIATED WITH POP EXPOSURE

摘要

Background Exposure to persistent organic pollutants (POPs) is associated with type 2 diabetes. Presence of the Ala allele in the peroxisome proliferator-activated receptor-gamma (PPARG) gene has been shown to be protective against type 2 diabetes, due to decreased accumulation of adipose mass. AIMS The objective is to study whether the presence of the Ala allele is protective against increased risk of type 2 diabetes associated with POP exposure among Finnish elderly subjects.METHODS The original birth cohort consists of 8,760 people born as singletons at the Helsinki University Central Hospital during 1934-1944. From the original study cohort, 2,003 men and women were selected at random to attend a clinical examination in 2003. The examination included a standard 2-h 75-g oral glucose tolerance test (0, 30 and 120 min), and blood sampling. WHO 2009 diagnostic criteria for type 2 diabetes and glucose regulation were used. Regression analyses were adjusted for age, sex, and waist circumference. The serum concentrations of oxychlordane, trans-nonachlor, p,p′-DDE, and PCB 153 were transformed into normalized ranks, summed, and categorized using 25th and 75th percentiles as cutoff points.RESULTS The frequency of Ala allele was 18% and the median serum concentrations of oxychlordane, trans-nonachlor, p,p′-DDE, and PCB 153 were 11, 28, 470, and 287 pg/g of lipid, respectively. High POP exposure was positively associated with type 2 diabetes, among both carriers with (OR=2.8, p=0.003) and without (OR=1.7, p=0.025) the Ala allele. However, POP exposure was associated with impaired fasting glucose among carriers (OR=2.8, p=0.002), whereas among non-carriers the association was inverse but non-significant (OR=0.38, p=0.14). POP exposure was not associated with glucose secretion, but significantly decreased insulin secretion during OGTT regardless of PPARG genotype.CONCLUSIONS Association between POPs and type 2 diabetes and early signs of impaired glucose metabolism is irrespective of PPARG polymorphism.