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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 a... Full description

Journal Title: Human Mutation January 2009, Vol.30(1), pp.49-55
Main Author: Chen, Pei
Other Authors: Jou, Yuh‐Shan , Fann, Cathy Sj , Chen, Jaw‐Wen , Chung, Chia‐Min , Lin, Chin‐Yu , Wu, Sheng‐Yeu , Kang, Mei‐Jyh , Chen, Ying‐Chuang , Jong, Yuh‐Shiun , Lo, Huey‐Ming , Kang, Chih‐Sen , Chen, Chien‐Chung , Chang, Huan‐Cheng , Huang, Nai‐Kuei , Wu, Yi‐Lin , Pan, Wen‐Harn
Format: Electronic Article Electronic Article
Language: English
Subjects:
Lpl
ID: ISSN: 1059-7794 ; E-ISSN: 1098-1004 ; DOI: 10.1002/humu.20812
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title: Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides
format: Article
creator:
  • Chen, Pei
  • Jou, Yuh‐Shan
  • Fann, Cathy Sj
  • Chen, Jaw‐Wen
  • Chung, Chia‐Min
  • Lin, Chin‐Yu
  • Wu, Sheng‐Yeu
  • Kang, Mei‐Jyh
  • Chen, Ying‐Chuang
  • Jong, Yuh‐Shiun
  • Lo, Huey‐Ming
  • Kang, Chih‐Sen
  • Chen, Chien‐Chung
  • Chang, Huan‐Cheng
  • Huang, Nai‐Kuei
  • Wu, Yi‐Lin
  • Pan, Wen‐Harn
subjects:
  • Young‐Onset Hypertension
  • Endophenotype
  • Lpl
  • Linkage Disequilibrium
  • Haplotype
ispartof: Human Mutation, January 2009, Vol.30(1), pp.49-55
description: 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 (), 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 , 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
language: eng
source:
identifier: ISSN: 1059-7794 ; E-ISSN: 1098-1004 ; DOI: 10.1002/humu.20812
fulltext: fulltext
issn:
  • 1059-7794
  • 10597794
  • 1098-1004
  • 10981004
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titleLipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides
creatorChen, Pei ; Jou, Yuh‐Shan ; Fann, Cathy Sj ; Chen, Jaw‐Wen ; Chung, Chia‐Min ; Lin, Chin‐Yu ; Wu, Sheng‐Yeu ; Kang, Mei‐Jyh ; Chen, Ying‐Chuang ; Jong, Yuh‐Shiun ; Lo, Huey‐Ming ; Kang, Chih‐Sen ; Chen, Chien‐Chung ; Chang, Huan‐Cheng ; Huang, Nai‐Kuei ; Wu, Yi‐Lin ; Pan, Wen‐Harn
ispartofHuman Mutation, January 2009, Vol.30(1), pp.49-55
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subjectYoung‐Onset Hypertension ; Endophenotype ; Lpl ; Linkage Disequilibrium ; Haplotype
descriptionPreviously, 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 (), 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 , 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 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 intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Hum Mutat 0,1–7, 2008. © 2008 Wiley‐Liss, Inc.
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titleLipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides
descriptionPreviously, 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 (), 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 , 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 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 intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Hum Mutat 0,1–7, 2008. © 2008 Wiley‐Liss, Inc.
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abstractPreviously, 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 (), 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 , 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 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 intronic variants may be associated with development of the hypertension endophenotype with elevated TG. Hum Mutat 0,1–7, 2008. © 2008 Wiley‐Liss, Inc.
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