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

Abstract

BackgroundTo 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/MethodsThe 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.ResultsThe 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).ConclusionsThe 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.

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

“…37 In addition, it was found that IGF-1 may induce lymphangiogenesis and facilitates lymphatic metastasis, 38 and be associated with larger tumor size, local LNM, and worse prognosis in cancers. Wang et al 41 reported that the G allele of rs5742612 was found to be associated with decreased insulin sensitivity and increased insulin secretion. In this study, we found that IGF1 rs5742612 A > G polymorphism might increase the risk of LNM among patients with EGJA.…”

Dietary Acid Load and Its Interaction With IGF1 and IL6 Polymorphisms on Metabolic Traits Among Postmenopausal Women

“…Thirdly, acid-base homeostasis may in uence calcium and magnesium absorption in the kidney [56] and consequences of serum calcium and magnesium were related to insulin sensitivity [57,58]. Finally, yet importantly, metabolic acidosis may reduce the secretion of IGF-I [59] and inhibit insulin sensitivity [60]. On the other hand, this nding was incongruent with a longitudinal study involved 911 older non-diabetic community-dwelling Swedish men [33].…”

Dietary Acid Load and Its Interaction with IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) Polymorphisms on Metabolic Traits among Postmenopausal Women

“…Thirdly, acid–base homeostasis may influence calcium and magnesium absorption in the kidney [ 70 ] and consequences of serum calcium and magnesium are related to insulin sensitivity [ 71 , 72 ]. Finally, yet importantly, metabolic acidosis may reduce the secretion of IGF-I [ 73 ] and inhibit insulin sensitivity [ 74 ]. On the other hand, this finding was incongruent with a longitudinal study involving 911 older non-diabetic community-dwelling Swedish men [ 34 ].…”