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

Abstract

We recently reported that rs361072, a promoter C/T variant of p110beta, 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.

• Authors: Karine Clément, Catherine Le Stunff, Aline Meirhaeghe, Agnès Dechartres, Jean Ferrieres, Arnaud Basdevant, Christian Boitard, Philippe Amouyel, Pierre Bougnères
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 96 Issue 3 Pg. 129-32 (Mar 2009) ISSN: 1096-7206 [Electronic] United States
• PMID: 19097921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Class I Phosphatidylinositol 3-Kinases
• PIK3CB protein, human

Topics

• Adult
• Class I Phosphatidylinositol 3-Kinases
• Cohort Studies
• Diabetes Mellitus, Type 2 (genetics)
• Female
• Genetic Variation
• Genotype
• Humans
• Insulin Resistance (genetics)
• Male
• Middle Aged
• Obesity (genetics)
• Phosphatidylinositol 3-Kinases (genetics)
• Promoter Regions, Genetic
• White People (genetics)