Lipoprotein lipase gene is linked and associated with hypertension in Taiwan young-onset hypertension genetic study

Pei Chen, Yuh Shan Jou, Cathy S.J. Fann, Jaw Wen Chen, Sheng Yeu Wu, Wen Harn Pan

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17 Citations (Scopus)

Abstract

Hypertriglyceridemia has been extensively associated with hypertension. However, the mechanism behind it is poorly understood. A positive linkage signal between Lipoprotein lipase (LPL) and young-onset hypertension has been identified by us as the strongest among 18 candidate genes. Here we report our fine mapping works with seven microsatellite markers flanking LPL, sequencing results for its promoter and exons, and an extended association study with the identified single nucleotide polymorphisms(SNP). First, using data from 213 individuals in 59 nuclear families of young-onset hypertension, multipoint analysis revealed a NPL score of 3.02 for the LPL (GZ-14/GZ-15) marker in intron 6. LPL marker (p < 10-12) and the haplotypes containing its allele 1 (p < 0.0001) were also significantly associated with young hypertension by transmission disequilibrium test. In-depth sequencing revealed no mutation in promoter and exon regions, except two cSNP: 7754C → A (C/A: 0.91/0.09), a silent mutation in exon 8 and S447X (C/G: 0.92/0.08), a stop codon mutation in exon 9. Other 11 cSNPs documented in NCBI GenBank are absent in our sample. Constructed from the above 2 cSNPs, haplotype AC showed a moderate TDT association with elevated triglyceride (p=0.02) and with hypertension and elevated triglyceride combined (p=0.06). Again, in an extended case-control study, a significant association was found between S447X and patients with persistent hypertension and elevated triglyceride (p=0.02). We conclude that LPL variants may play a causal role in the development of hypertension in Taiwan Han Chinese. The moderate association with SNP haplotype suggests that other regulatory LPL variant may exist.

Original languageEnglish
Pages (from-to)651-658
Number of pages8
JournalJournal of Biomedical Science
Volume12
Issue number4
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

Keywords

  • Haplotype
  • Linkage
  • Lipoprotein lipase
  • S447X
  • SNP
  • Transmission disequilibrium test
  • Young-onset hypertension

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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