제2형 당뇨병환자에서의 인슐린양 성장인자 결합단백질-3(IGFBP-3) promoter -202 A/C 유전자 다형성

Abstract

Backgrounds: IGFs share approximately 50 percent of their amino acid with insulin and are largely bound to IGFBP-3, and they are known to be important in glucose metabolism. We evaluated the impact of IGFBP-3 promoter-202 polymorphism on concentration of IGF-I and IGFBP-3, and its relationship with different clinical characteristics of type 2 diabetes (T2DM). Method: A single nucleotide polymorphism at -202 locus of the IGFBP-3 promoter was genotyped for T2DM patients and the controls in their forties. Then, we compared concentrations of IGF-I and IGFBP-3, IGFBP-3 promoter-202 polymorphisms, and other clinical characteristics between diabetes group and the control. Results: Total of 169 subjects were enrolled. IGF-I levels of diabetes group were lower than those of the control, while IGFBP-3 levels of diabetes group were higher than the control. Among IGFBP-3 promoter -202 polymorphisms, AA occurred in 31 subjects (42.5%), AC in 33 (45.2%), and CC in 20 (27.4%) in control group. IGFBP-3 level was highest in AA group and lowest in CC group, and, IGF-I/IGFBP-3 molar ratio was lower in AA group than AC and CC groups. In diabetes group, AA occurred in 42 patients (50%) and AC in 42 patients (50%) without any significant difference between the two groups. IGF-I was in a negative correlation with weight, height, BMI and FBS. And IGFBP-3 correlated positively with BMI, FBS, and cholesterol. Conclusion: T2DM patients had decreased levels of IGF-I and increased levels of IGFBP-3, which can reduce IGF-I/IGFBP-3 molar ratio and free IGF-I. In other words, low free IGF-I level can give rise to T2DM. IGFBP-3 promoter -202 genotype has a control over concentration of IGFBP-3, but not weight, height, and BMI. However, IGFBP-3 is in a positive correlation with BMI. Thus, we propose that IGFBP-3 promoter -202 genotype may influence glucose metabolism not only by directly controlling IGFBP-3 concentration, but also through BMI indirectly.