Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with lipid profiles in Chinese hypertensive families.
Elevated TG [triacylglycerol (triglyceride)] is a significant independent risk factor for cardiovascular disease. LPL (lipoprotein lipase) is one of the key enzymes in the metabolism of the TG-rich lipoproteins which hydrolyses TG from the chylomicrons and very-LDL (low-density lipoprotein). To investigate the relationship between the LPL gene and lipid profiles, especially TG, in 148 hypertensive families, we have chosen seven flanking microsatellite markers and four internal markers of the LPL gene and conducted linkage analysis by SOLAR and S.A.G.E. (statistical analysis for genetic epidemiology)/SIBPAL 2 programs, and linkage disequilibrium analysis by QTDT (quantitative transmission/disequilibrium test) and GOLD (graphical overview of linkage disequilibrium). There were statistically significant differences in lipid levels between subjects without and with hypertension within families. A maximum LOD score of 1.3 with TG at the marker D8S261 was observed by SOLAR. Using S.A.G.E./SIBPAL 2, we identified a linkage with TG at the marker 'ATTT' located within intron 6 of the LPL gene (P=0.0095). Two SNPs (single nucleotide polymorphisms), HindIII and HinfI, were found in linkage disequilibrium with LDL-cholesterol levels (P=0.0178 and P=0.0088 respectively). A strong linkage disequilibrium was observed between the HindIII in intron 8 and HinfI in the exon 9 (P<0.00001, D'=0.895). Linkage disequilibrium was also found between the 'ATTT' polymorphism in intron 6 and two SNPs (P=0.0021 and D'=0.611 for HindIII; and P=0.00004, D'=0.459 for HinfI). The present study in the Chinese families with hypertension suggested that the LPL gene might influence lipid levels, especially TG metabolism. Replication studies both in Chinese and other populations are warranted to confirm these results.
Division of Population Genetics and Prevention, Cardiovascular Institute, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
Wenjie
W
Yang
Jianfeng
J
Huang
Cailiang
C
Yao
Shaoyong
S
Su
Donghai
D
Liu
Dongliang
D
Ge
Dongfeng
D
Gu
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002681:China; D002784:Cholesterol / Q000097:blood; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D005819:Genetic Markers; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase