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In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes

2008; Elsevier BV; Volume: 96; Issue: 3 Linguagem: Inglês

10.1016/j.ymgme.2008.11.160

1096-7206

Karine Clément, Catherine Le Stunff, Aline Meirhaeghe, Agnès Dechartres, Jean Ferrières, Arnaud Basdevant, Christian Boîtard, Philippe Amouyel, Pierre Bougnères,

Metabolism, Diabetes, and Cancer

We recently reported that rs361072, a promoter C/T variant of p110β, the catalytic subunit of PI3-kinase, was associated with a protection from insulin resistance (IR) in Caucasian adolescents in proportion of their body mass. We tested if this cis-regulatory QTL is associated with IR and type 2 diabetes in 7885 middle-aged obese and non-obese adults of European ancestry. We genotyped rs361072 in 1139 non-diabetic obese (NDO) European adults, in whom IR was estimated by the HOMA-IR index. We also studied 427 type 2 diabetic obese adults (DO) and 424 diabetic non-obese (DNO) adults to test whether their disease status was associated with a decreased prevalence of the protective variant. The prevalence of rs361072 and association with IR was also examined in 5895 non-obese non-diabetic adults (NDNO). rs361072 was associated with HOMA-IR (p = 4 · 10−4) in NDO, so that C/C patients had a 17% decrease of this index (p = 0.002). A statistical trend (p = 1.1 · 10−2) for the same genotypic differences was also observed in NDNO adults, but of insignificant magnitude (4.2%). The distribution of rs361072 genotype was comparable in NDO, DO, DNO and NDNO individuals. Allele C of rs361072 is associated with a protection from IR in obese and non-obese adults, but has no significant effect, however, on diabetes risk in obese or non-obese Europeans.