title: Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.
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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan, R.O.C.
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Sheng-Yeu
authors.initials: SY
authors.lastname: Wu
authors.forename: Mei-Jyh
authors.initials: MJ
authors.lastname: Kang
authors.forename: Ying-Chuang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yuh-Shiun
authors.initials: YS
authors.lastname: Jong
authors.forename: Huey-Ming
authors.initials: HM
authors.lastname: Lo
authors.forename: Chih-Sen
authors.initials: CS
authors.lastname: Kang
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Chen
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
authors.forename: Nai-Kuei
authors.initials: NK
authors.lastname: Huang
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Wu
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
mesh_terms: 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
chemical_list: D014280:Triglycerides; D008071:Lipoprotein Lipase