Abstract
The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and body mass index (BMI) and three single nucleotide polymorphisms (SNP)s in the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) gene. We were also interested in whether these associations differed by tertiles of diet, physical activity or presence of polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene among Hispanics and Non-Hispanic Whites (NHW) from Colorado. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 NHW pedigrees (1240 families) from the San Luis Valley and Denver. We genotyped the Gly482Ser, Thr528Thr and Thr612Met polymorphisms in the PGC-1α gene and the Pro12Ala polymorphism of the PPAR-γ gene. Historical physical activity (average METS/week) as well as average dietary intake over the past year was assessed by self-report. Data were analyzed using the Family Based Association Test (FBAT) as well as generalized estimating equations (GEE). We did not find any significant association between three SNPs in the PGC-1α gene and T2DM in Hispanics or NHW; however, using FBAT, we found the common Thr612Thr allele of the PGC-1α gene to be associated with T2DM among Hispanic subjects carrying the rare Pro12Ala allele of the PPAR-γ gene (p=.003). We found similar associations when we considered a haplotype containing that allele (p=.002). However, the results of the GEE analysis did not confirm these findings: odds ratio (OR)=1.68, 95% CI (0.5, 5.2) suggesting these results may due to chance. BMI also did not show any consistent associations with the PGC-1α gene. In conclusion, we did not find an association between the PGC-1α gene and T2DM or BMI and there were no consistent interactions with diet, physical activity or the Pro12Ala polymorphism of the PPAR-γ gene.
Key words
type 2 diabetes - gene - environment interaction - Hispanic
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Correspondence
T. L. Nelson
Colorado State University
Department of Health and Exercise Science
223 Moby
Fort Collins
CO 80523
Phone: 970/491 63 20
Fax: 970/491 04 45
Email: tnelson@cahs.colostate.edu