APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals.
BACKGROUND
Apolipoprotein A-I gene (APOA1) polymorphisms have been associated with variations in serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol. We have investigated whether APOA1 common variants are also associated with variations in basal triglyceride serum concentrations and response to atorvastatin in individuals with hypercholesterolemia.


METHODS
APOA1 G-75A and C83T polymorphisms and variations in serum lipids were evaluated in 150 hypercholesterolemic (HC) and 93 normolipidemic (NL) unrelated European-derived Brazilians treated with atorvastatin (10 mg/day for 4 weeks). Genomic DNA was extracted from blood leukocytes using a salting-out method and APOA1 polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
G-75A polymorphism was associated with differences in serum concentrations of triglyceride and very low-density lipoprotein (VLDL)-cholesterol (p=0.026) in HC men. After atorvastatin treatment, women carrying the GG/CC haplotype had lower serum triglyceride and VLDL-cholesterol (p=0.020) than non-carriers. In men, the reduction in serum triglyceride in response to atorvastatin was found to be slightly lower in GG/CC haplotype carriers (p=0.051).


CONCLUSIONS
Our data suggest that APOA1 polymorphisms are associated with variations of baseline serum concentrations of triglyceride and VLDL-cholesterol and in response to atorvastatin in a gender-specific manner.
Sorkin
Simone C
SC
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Forestiero
Francisco J
FJ
Hirata
Mario H
MH
Guzmán
Elizabeth C R
EC
Cavalli
Selma A
SA
Bertolami
Marcelo C
MC
Salazar
Luis A
LA
Hirata
Rosario D C
RD
D016632:Apolipoprotein A-I / Q000235:genetics*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D014644:Genetic Variation; D023281:Genomics; D006239:Haplotypes; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D012737:Sex Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin