A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster.
In patients with premature coronary heart disease, the most common lipoprotein abnormality is high-density lipoprotein (HDL) deficiency. To assess the genetic background of the low HDL-cholesterol trait, we performed a candidate gene study in 25 families with low HDL, collected from the genetically isolated population of Finland. We studied 21 genes encoding essential proteins involved in the HDL metabolism by genotyping intragenic and flanking markers for these genes. We found suggestive evidence for linkage in two candidate regions: Marker D1S2844, in the apolipoprotein A-II (APOA2) region, yielded a LOD score of 2.14 and marker D11S939 flanking the apolipoprotein A-I/C-III/A-IV gene cluster (APOA1C3A4) produced a LOD score of 1.69. Interestingly, we identified potential shared haplotypes in these two regions in a subset of low HDL families. These families also contributed to the obtained positive LOD scores, whereas the rest of the families produced negative LOD scores. None of the remaining candidate regions provided any evidence for linkage. Since only a limited number of loci were tested in this candidate gene study, these LOD scores suggest significant involvement of the APOA2 gene and the APOA1C3A4 gene cluster, or loci in their immediate vicinity, in the pathogenesis of low HDL.
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Heidi E
HE
Lilja
Aino
A
Soro
Kati
K
Ylitalo
Ilpo
I
Nuotio
Jorma S A
JS
Viikari
Veikko
V
Salomaa
Erkki
E
Vartiainen
Marja-Riitta
MR
Taskinen
Leena
L
Peltonen
Päivi
P
Pajukanta
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D016633:Apolipoprotein A-II / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005387:Finland; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D013631:Tangier Disease / Q000235:genetics* / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D005819:Genetic Markers