An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance.
OBJECTIVE
Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects.


METHODS
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.
Rietveld
I
I
Department of Internal Medicine, Rotterdam, The Netherlands.
Hofman
A
A
Pols
H A P
HA
van Duijn
C M
CM
Lamberts
S W J
SW
Janssen
J A M J L
JA
D000368:Aged; D000419:Albuminuria / Q000453:epidemiology* / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D018149:Glucose Intolerance / Q000453:epidemiology* / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D007334:Insulin-Like Growth Factor I