Is apolipoprotein(a) a susceptibility gene for Type I diabetes mellitus and related to long-term survival?

Aims/hypothesis. High lipoprotein(a) [Lp(a)] plasma concentrations are a ge netically determined risk factor for atherosclerotic complications. In heal thy subjects Lp(a) concentrations are mostly controlled by the apolipoprote in(a) [apo(a)] gene locus which determines a size polymorphism with more th an 30 alleles. Subjects with low molecular weight apo(a) phenotypes on aver age have higher Lp(a) concentrations than those with high molecular weight apo(a) phenotypes. There are many opinions about whether and why Lp(a) is r aised in patients with Type I diabetes (insulin-dependent) mellitus. Methods. We investigated Lp(a) plasma concentrations and apo(a) phenotypes in 327 patients with Type I diabetes mellitus (disease duration 1-61 years) and in 200 control subjects matched for age and sex. Results. Patients wit h a disease duration of up to 15 years had significantly higher Lp(a) conce ntrations (24.3 +/- 34.0 mg/dl vs 16.7 +/- 22.6mg/dl, p = 0.014) compared w ith control subjects. This increase can be explained by a considerably high er frequency of low molecular weight apo(a) phenotypes (38.9 % vs 23.5 %, p < 0.005). The frequency of low molecular weight apo(a) phenotypes decrease d continuously with disease duration from 41.7% in those with disease durat ion of up to 5 years to 18.2 % in those with the disease lasting more than 35 years. Conclusion/interpretation. Our data show that an increase of Lp(a) in Type I diabetic patients can only be observed in groups with short diabetes dura tion and that this elevation is genetically determined. Therefore, the apo( a) gene, located at 6q26-27, might be a susceptibility gene for Type I diab etes mellitus which is supported by recently published studies reporting ev idence for linkage of this region (6q27) with Type I diabetes mellitus. Fur thermore, the decreasing frequency of low molecular weight apo(a) phenotype s with disease duration suggests a survivor effect.