Concordant association of lipid gene variation with a combined HDL/LDL-cholesterol phenotype in two European populations.
OBJECTIVE
SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach.


METHODS
Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes.


RESULTS
Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence.


CONCLUSIONS
This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait.
Bauerfeind
Anja
A
Department of Bioinformatics, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
Knoblauch
Hans
H
Costanza
Michael C
MC
Luganskaja
Tatjana
T
Toliat
Mohammad R
MR
Nürnberg
Peter
P
Luft
Friedrich C
FC
Reich
Jens G
JG
Morabia
Alfredo
A
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000235:genetics*; D008078:Cholesterol, LDL / Q000235:genetics*; D005260:Female; D005858:Germany; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics; D013557:Switzerland; D044465:White People
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins; D049294:Phospholipid Transfer Proteins; D011973:Receptors, LDL