Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.
Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG.
Chen
Pei
P
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan, R.O.C.
Jou
Yuh-Shan
YS
Fann
Cathy S J
CS
Chen
Jaw-Wen
JW
Chung
Chia-Min
CM
Lin
Chin-Yu
CY
Wu
Sheng-Yeu
SY
Kang
Mei-Jyh
MJ
Chen
Ying-Chuang
YC
Jong
Yuh-Shiun
YS
Lo
Huey-Ming
HM
Kang
Chih-Sen
CS
Chen
Chien-Chung
CC
Chang
Huan-Cheng
HC
Huang
Nai-Kuei
NK
Wu
Yi-Lin
YL
Pan
Wen-Harn
WH
D017668:Age of Onset; D016022:Case-Control Studies; D005192:Family Health; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D015228:Hypertriglyceridemia / Q000235:genetics*; D007438:Introns; D015810:Linkage Disequilibrium; D008071:Lipoprotein Lipase / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D014280:Triglycerides / Q000097:blood* / Q000235:genetics
D014280:Triglycerides; D008071:Lipoprotein Lipase