Artigo Revisado por pares

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

ISSN

1096-7206

Autores

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

Tópico(s)

Metabolism, Diabetes, and Cancer

Resumo

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.

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