Is apolipoprotein(a) a susceptibility gene for type I diabetes mellitus and related to long-term survival?
OBJECTIVE
High lipoprotein(a) [Lp(a)] plasma concentrations are a genetically determined risk factor for atherosclerotic complications. In healthy subjects Lp(a) concentrations are mostly controlled by the apolipoprotein(a) [apo(a)] gene locus which determines a size polymorphism with more than 30 alleles. Subjects with low molecular weight apo(a) phenotypes on average 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 raised 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 with a disease duration of up to 15 years had significantly higher Lp(a) concentrations (24.3 +/- 34.0 mg/dl vs 16.7 +/- 22.6 mg/dl, p = 0.014) compared with control subjects. This increase can be explained by a considerably higher 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 decreased continuously with disease duration from 41.7% in those with disease duration of up to 5 years to 18.2% in those with the disease lasting more than 35 years.


CONCLUSIONS
Our data show that an increase of Lp(a) in Type I diabetic patients can only be observed in groups with short diabetes duration and that this elevation is genetically determined. Therefore, the apo(a) gene, located at 6q26-27, might be a susceptibility gene for Type I diabetes mellitus which is supported by recently published studies reporting evidence for linkage of this region (6q27) with Type I diabetes mellitus. Furthermore, the decreasing frequency of low molecular weight apo(a) phenotypes with disease duration suggests a survivor effect.
Kronenberg
F
F
Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Auinger
M
M
Trenkwalder
E
E
Irsigler
K
K
Utermann
G
G
Dieplinger
H
H
D000328:Adult; D000419:Albuminuria; D001054:Apolipoproteins A / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D005260:Female; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011507:Proteinuria; D012016:Reference Values; D017741:Survivors; D013997:Time Factors
D001054:Apolipoproteins A; D006442:Glycated Hemoglobin; D017270:Lipoprotein(a)