Lipoprotein lipase variants associated with an endophenotype of hypertension: Hypertension combined with elevated triglycerides

Pei Chen, Yuh Shan Jou, Cathy S.J. Fann, Jaw Wen Chen, Chia Min Chung, Chin Yu Lin, Sheng Yeu Wu, Mei Jyh Kang, Ying Chuang Chen, Yuh Shiun Jong, Huey Ming Lo, Chih Sen Kang, Chien Chung Chen, Huan Cheng Chang, Nai Kuei Huang, Yi Lin Wu, Wen Harn Pan

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalHuman Mutation
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2009
Externally publishedYes

Keywords

  • Endophenotype
  • Haplotype
  • Linkage disequilibrium
  • LPL
  • Young-onset hypertension

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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