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Gene encoding the catalytic subunit p110beta of human phosphatidylinositol 3-kinase: cloning, genomic structure, and screening for variants in patients with type 2 diabetes.

Phosphatidylinositol (PI) 3-kinase is a key signaling molecule in insulin-stimulated glucose transport. Therefore, we investigated the catalytic subunit p110beta, of human PI 3-kinase as a candidate gene for type 2 diabetes. Human p110beta gene was cloned from the placental genomic library. All 22 exons, intronic regions flanking the exons and 1.5 kb of the proximal/5' region of the p110beta gene, were screened for variants by single-strand conformation polymorphism analysis in 79 Finnish patients with type 2 diabetes . Allele frequencies of the variants were also determined in 77 nondiabetic control subjects. No variants were found in exons in diabetic patients. However, we identified two nucleotide polymorphisms in the proximal/5' region of the p110beta gene and a variation in the number of 2-bp repeat sequence (TA)n in intron 4. The allele frequencies did not differ between diabetic and control subjects. Our results may indicate that the catalytic subunit p110beta of PI 3-kinase plays such a fundamental role in the insulin-signaling pathway that structural variants are not likely to exist in that gene. The importance of the polymorphisms in the proximal/5' region of the p110beta gene for insulin signaling remains to be determined.