Microsatellite and Single Nucleotide Polymorphisms in the Insulin-Like Growth Factor 1 Promoter with Insulin Sensitivity and Insulin Secretion.

BACKGROUND To investigate associations of the CA microsatellite and rs35767, rs5742612, and rs2288377 polymorphisms and the single nucleotide polymorphism (SNP) haplotypes with and without the CA microsatellite in the IGF1 promoter with insulin sensitivity and secretion. MATERIAL AND METHODS The CA microsatellite and SNPs were genotyped in 389 type 2 diabetes mellitus (T2DM) patients. A 75 g oral glucose tolerance test (OGTT) was given to all the participants. Associations of the genotypes and haplotypes with insulin sensitivity, insulin secretion, glucose tolerance, and insulin-like growth factor 1 (IGF1) were analyzed by ANCOVA (general linear model) and multiple linear regression, after controlling for gender, age, and BMI. RESULTS The CA microsatellite, rs35767 polymorphisms, and SNP haplotypes with or without CA showed no significant association with metabolic parameters. The C allele of rs5742612 was found to be associated with decreased insulin sensitivity (HOMA-S index, β=-0.131, P=0.008; fasting insulin level, β=0.022, P=0.006) and increased insulin secretion (HOMA-B index, β=0.099, P=0.008; insulin AUC, β=0.112, P=0.012). The linear regression model also indicated that the A allele of rs2288377 was associated with decreased insulin sensitivity (HOMA-S index, β=-0.159, P=0.001; fasting insulin, β=0.143, P=0.001) and increased insulin secretion (HOMA-B index, β=0.114, P=0.017; insulin AUC, β=0.042, P=0.002). CONCLUSIONS The CA microsatellite and rs35767 have no genotype-related difference in insulin sensitivity or secretion. The rs5742612 and rs2288377 polymorphisms are significantly associated with insulin biology, with the TT genotype exhibiting higher insulin sensitivity and lower insulin secretion compared with carriers of the C allele and A allele, respectively, mostly attributed to the direct functional roles of the two loci.