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Obesity modifies the effects of the Asp905Tyr variant of PPP1R3A on risk of type 2 diabetes and insulin sensitivity
Author(s) -
Mammarella S.,
Creati B.,
Staniscia T.,
Verginelli F.,
Manzoli L.,
Di Valerio A.,
Aceto G.,
Romano F.,
Cama G.,
Capani F.,
Consoli A.,
Vitacolonna E.,
EspositoDel Puente A.,
Battista P.,
Della Loggia F.,
MarianiCostantini R.,
Quon M. J.,
Cama A.
Publication year - 2007
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2006.00699.x
Subject(s) - medicine , gerontology
Interactions between genetic and environmental factors cause insulin resistance leading to type 2 diabetes mellitus. Three frequent variants of the PPP1R3A gene (Arg883Ser, Asp905Tyr and ARE2/ARE1) encoding the regulatory subunit of PP1G associate with higher insulin sensitivity and lower prevalence of diabetes in Pima Indians [1]. No definitive associations between the Asp905Tyr variant and diabetes are observed in several studies conducted in Asian populations [2–5]. In the present study, we evalu- ated whether the two frequent variants of PPP1R3A detected in Caucasians (Asp905Tyr and ARE1/ARE2) interact with obesity in the pathogenesis of diabetes in an Italian population. Our study provides evidence that the Tyr905 variant of PPP1R3A is associated with higher insulin sensitivity and reduced risk of diabetes in the absence of obesity. Interestingly, the presence of obesity modifies the effect of this genotype to confer lower insu- lin sensitivity and a higher risk of diabetes