Myeloperoxidase gene sequence variations are associated with low-density-lipoprotein characteristics.
The small, dense low-density-lipoprotein (LDL) phenotype is associated with an increased atherosclerosis risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) for LDL peak-particle size (LDL-PPD) on the 17q21 region. This region encodes the myeloperoxidase (MPO) gene. MPO is able to oxidize LDL by its reactive intermediates. To test the associations between MPO gene polymorphisms and LDL-PPD as well as plasma lipid levels, we performed direct sequencing of the coding regions, exon-intron splicing boundaries, and the regulatory regions on 25 subjects to identify new genetic variants. Genotyping was performed either by TaqMan or direct sequencing on 680 subjects in the QFS. LDL-PPD was measured by gradient gel electrophoresis (GGE) on nondenaturing 2-16% polyacrylamide gradient gels. MPO gene sequencing revealed 16 polymorphisms. The c.-653G > A MPO polymorphism was associated with lower plasma total cholesterol, LDL cholesterol (LDL-C), and LDL apolipoprotein B (LDL-apoB) levels (P = 0.026, 0.042 and 0.014, respectively). No significant association with a gene-dosage effect were observed for LDL-PPD. The MPO gene variants are not associated with LDL-PPD and thus are unlikely to be responsible for the quantitative trait locus reported on 17q21. However, the c.-653G > A is associated with plasma LDL-C and LDL-apoB concentrations.
Dolley
Guillaume
G
CRML, CHUL Research Center, 2705 Laurier Blvd, Quebec, G1V-4G2, Canada.|Department of Food Science and Nutrition, Laval University, Quebec, Canada.|Nutraceuticals and Functional Foods Institute (INAF), Quebec, Canada.
Lamarche
Benoit
B
Department of Food Science and Nutrition, Laval University, Quebec, Canada.|Nutraceuticals and Functional Foods Institute (INAF), Quebec, Canada.
Després
Jean-Pierre
JP
Québec Heart Institute, Quebec, Canada.|Department of Social and Preventive Medicine, Laval University, Quebec, Canada.
Bouchard
Claude
C
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Pérusse
Louis
L
CRML, CHUL Research Center, 2705 Laurier Blvd, Quebec, G1V-4G2, Canada.|Department of Social and Preventive Medicine, Laval University, Quebec, Canada.
Vohl
Marie-Claude
MC
CRML, CHUL Research Center, 2705 Laurier Blvd, Quebec, G1V-4G2, Canada. Marie-Claude.Vohl@crchul.ulaval.ca.|Department of Food Science and Nutrition, Laval University, Quebec, Canada. Marie-Claude.Vohl@crchul.ulaval.ca.|Nutraceuticals and Functional Foods Institute (INAF), Quebec, Canada. Marie-Claude.Vohl@crchul.ulaval.ca.
D019943:Amino Acid Substitution; D001055:Apolipoproteins B / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry*; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008077:Lipoproteins, LDL; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C019455:low density lipoprotein inhibitor; D009195:Peroxidase