[Candidate genes and polymorphism analysis in type 2 diabetes mellitus].
OBJECTIVE
Diabetes mellitus type 2 is a polygenic disease. Up to now, numerous candidate genes have been examined and tested for their association to metabolic parameters and late complications of diabetes. Between 2000 to 2004, polymorphisms of the following genes and their association to metabolic parameters and late complications of diabetes were examined in the authors' laboratory: PAI-1 (plasminogen activator inhibitor-1), PPARgamma2 (peroxisome proliferator-activated receptor gamma2), UCP-1 (uncoupling protein-1), and adiponectin. Based on this, the question was examined whether the combination of the respective rarely occurring genotypes results in an increased atherogenic risk and a higher prevalence of micro- and macrovascular late complications of diabetes.


METHODS
Subjects were enrolled from a cohort of 570 type 2 diabetic patients (246 female and 324 male, mean age 66.9+/-9.2 years) who had participated in a population-based study on diabetes and its complications in a mobile survey unit in 23 towns and villages in Bavaria (Germany). Retinopathy was diagnosed by nonmydriatic fundus photography (Canon CR4-45 NM). Photographs of the retina of both eyes (one photo per eye) were taken. Data on macrovascular complications of diabetes were obtained using a standardized questionnaire.


RESULTS
A significant association between the number of rarely occurring genotype combinations and the following parameters could be described: diastolic blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and grade of retinopathy.


CONCLUSIONS
An accumulation of certain genotypes of candidate genes for diabetes mellitus type 2 is associated with the severity of dyslipidemia and microvascular late complications, e.g., grade of retinopathy. Therefore, screening for genotype combinations of these metabolic target genes might offer the opportunity to identify diabetic patients at a high risk for macro- and microvascular complications.
Zietz
Bettina
B
Innere Medizin II, Kreiskrankenhaus, Kelheim, Germany. bettina.zietz@kkh-kelheim.de
Leonhardt
Katrin
K
Schäffler
Andreas
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015992:Body Mass Index; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004247:DNA / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000235:genetics*; D050171:Dyslipidemias / Q000150:complications; D005091:Exons / Q000235:genetics; D005260:Female; D005654:Fundus Oculi; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D011795:Surveys and Questionnaires
D004247:DNA