An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance

Eur J Endocrinol. 2006 May;154(5):715-21. doi: 10.1530/eje.1.02144.

Abstract

Objective: Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects.

Design: We investigated whether a polymorphism near the promoter region of the IGF-I gene was related to the development of MA.

Methods: For this study, 1069 participants of the Rotterdam study were selected (440 participants with an abnormal glucose tolerance (AGT), 220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595 subjects with a normal glucose tolerance (NGT).

Results: 787 subjects were carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2-7.7); P = 0.02) in variant carriers with AGT than in carriers of the wild type of this IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2-4.0); P = 0.009). Compared with wild type carriers with AGT, the relative risk for MA was unadjusted and non-significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8-2.9). However, after adjustment for possible confounding factors (age, gender, mean blood pressure, fasting insulin, fasting glucose and smoking) this risk became significant (OR: RR 2.1; 95% CI:1.1-4.4; P = 0.04).

Conclusions: In subjects with AGT, a higher risk for MA was observed in variant carriers than in carriers of the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily associated with cardiovascular disease in subjects with AGT, our study suggests that variant carriers have a higher risk for cardiovascular disease than carriers of the wild type when they develop an AGT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / epidemiology*
  • Albuminuria / genetics*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Glucose Intolerance / epidemiology*
  • Glucose Intolerance / genetics*
  • Glucose Tolerance Test
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prevalence
  • Promoter Regions, Genetic
  • Risk Factors

Substances

  • Insulin-Like Growth Factor I