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Association of beta3 adrenergic receptor and peroxisome proliferator-activated receptor gamma 2 polymorphisms with insulin sensitivity: a twin study.

OBJECTIVE
To study the effect of beta3 adrenergic receptor (beta3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPARgamma2) Prol2Ala polymorphisms on insulin resistance.


METHODS
One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity.


RESULTS
The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Prol2Pro, Prol2Ala, and Alal2Ala were 89.9%, 9.6%, and 0.5%, respectively. For beta3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA-IR had statistic significance. For PPARgamma2 Pro12Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS.


CONCLUSIONS
Beta3AR Trp64Arg and PPARgamma2 Pro12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.