Clinical Diabetes 2006;7(2):169-180.
제2형 당뇨병환자에서의 인슐린양 성장인자 결합단백질-3 (IGFBP-3) promoter -202 A/C 유전자 다형성
남지선, 공지현, 노태웅, 김철식, 박종숙, 김혜진, 최유경, 임재윤, 강은석, 안철우, 차봉수, 이은직, 임승길, 김경래, 이현철
Genetic Polymorphism of Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) Promoter Gene in Type 2 DM patients
Ji Sun Nam, Ji Hyun Kong, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Hye Jin Kim, You Kyoung Choi, Jae Yun Lim, Eun Seok Kang, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee
Abstract
Background
s: 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.
Key Words: Insulin-Like growth factor, Insulin-Like growth factor binding protein-3, Insulin-Like growth factor binding protein-3 promoter -202 polymorphism, Type 2 diabetes mellitus
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