Common sequence variant in lipoprotein lipase gene conferring triglyceride response to fibrate treatment.
OBJECTIVE
Little is known about whether the variations in the lipoprotein lipase (LPL) and apolipoprotein gene cluster (APOA1/C3/A5) confer appreciable triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.


METHODS
We investigated whether variations in these genes confer a triglyceride lowering response after fibrate treatment among 145 patients with hypertriglyceridemia receiving 6 months of fibrate treatment.


RESULTS
Overall triglycerides decreased from 746.2 mg/dl to 465.9 mg/dl and the mean percentage of triglyceride lowering was 50.7 +/- 38.6%. A total of two polymorphisms, LPL IVS8 +483T>G and APOA1 +2169G>C, were associated with a significant percentage of triglyceride lowering. Common haplotype effects of LPL on the triglyceride lowering percentage were significant (p = 0.002) and the percentage of variance explained by the LPL haplotype was 7.5%. One common LPL haplotype encompassing three polymorphisms was associated with a -45.40% change (p < 0.001) and risk of a 5.9-fold risk for developing a poor response (95% confidence interval: 1.11-31, p = 0.037), compared with the most frequent LPL haplotype.


CONCLUSIONS
Our results indicate that the LPL gene variant may cause triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.
Chien
Kuo-Liong
KL
Institute of Preventive Medicine, School of Preventive Medicine, National Taiwan University, Taiwan.
Lin
Yen-Lin
YL
Wen
Hui-Chin
HC
Lin
Hsing-Pei
HP
Yen
Ching-Tzu
CT
Lin
Shu-Wha
SW
Kao
Jau-Tsuen
JT
D001053:Apolipoproteins / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002994:Clofibrate / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007438:Introns; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000378:metabolism*
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase; D002994:Clofibrate