GDF15 (growth-differentiation factor 15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy. In the present study, we have investigated the relationship between GDF15 gene variants and left ventricular hypertrophy in human essential hypertension. A community-based hypertensive population sample of 1527 individuals (506 men and 1021 women) was genotyped for three GDF15 genetic variants, including one tag variant −3148C>G (rs4808793) and two exonic variants +157A>T (rs1059369) and +2438C>G (rs1058587). The effects of those variants on gene expression were studied by use of luciferase reporter assays and the determination of plasma GDF15 levels. Only the tag variant −3148G was significantly associated with a lower risk of left ventricular hypertrophy [odds ratio=0.75 (95% confidence interval, 0.63–0.89); P=0.0009]. Multiple regression analyses confirmed that −3148G predicted the decrease in left ventricular end-diastolic diameter (β=−0.10, P=0.0001), end-systolic diameter (β=−0.09, P=0.0007), mass (β=−0.11, P<0.0001) and indexed mass (β=−0.12, P<0.0001). These effects were independent of conventional factors, including gender, age, body surface area, blood pressure, diabetes, cigarette smoking and alcohol consumption. The transcription activity of the −3148G-containing construct was increased 1.45-fold (P=0.015) at baseline and 1.73-fold (P=0.008) after stimulation with phenylephrine when compared with the −3148C construct. The −3148G allele was also associated with a significant increase in the plasma GDF15 level in hypertensive subjects (P=0.04). In conclusion, the results show that a promoter haplotype containing the −3148G variant increases GDF15 transcription activity and is associated with favourable left ventricular remodelling in human essential hypertension.
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Research Article|
October 19 2009
The haplotype of the growth-differentiation factor 15 gene is associated with left ventricular hypertrophy in human essential hypertension
Xiaojian Wang;
Xiaojian Wang
1
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Xu Yang;
Xu Yang
1
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Kai Sun;
Kai Sun
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Jingzhou Chen;
Jingzhou Chen
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Xiaodong Song;
Xiaodong Song
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Hu Wang;
Hu Wang
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Zhe Liu;
Zhe Liu
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Changxin Wang;
Changxin Wang
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Channa Zhang;
Channa Zhang
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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Rutai Hui
1Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, FuWai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
Correspondence: Dr Rutai Hui (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 02 2008
Revision Received:
May 29 2009
Accepted:
June 08 2009
Accepted Manuscript online:
June 08 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (2): 137–145.
Article history
Received:
December 02 2008
Revision Received:
May 29 2009
Accepted:
June 08 2009
Accepted Manuscript online:
June 08 2009
Citation
Xiaojian Wang, Xu Yang, Kai Sun, Jingzhou Chen, Xiaodong Song, Hu Wang, Zhe Liu, Changxin Wang, Channa Zhang, Rutai Hui; The haplotype of the growth-differentiation factor 15 gene is associated with left ventricular hypertrophy in human essential hypertension. Clin Sci (Lond) 15 January 2010; 118 (2): 137–145. doi: https://doi.org/10.1042/CS20080637
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