Histidine decarboxylase (HDC) is a key determinant of the levels of endogenous histamine
that has long been recognized to play important pathophysiological roles during development
of chronic heart failure (CHF). Meanwhile, certain genetic variants in HDC gene were reported to affect the function of HDC and associated with histamine-related
diseases. However, the relation between polymorphisms of HDC gene and CHF risk remains unclear. This study aims to investigate the associations
between 2 nonsynonymous HDC polymorphisms (rs17740607 and rs2073440) and CHF. We designed a 2-stage case–control
study, in which we genotyped 439 patients with CHF and 467 healthy controls recruited
in Xi'an, China, and replicated this study in 413 patients with CHF and 452 healthy
subjects in Kunming, China. We also performed in vitro experiments to further validate
the functional consequences of variants positively associated with CHF. The rs17740607
polymorphism showed replicated associations with all-cause CHF according to genotype
and allele distribution and also under a dominant and additive genetic model after
adjusted for traditional cardiovascular-related factors. Functional experiments further
demonstrated that rs17740607 polymorphism decreased the HDC activity. In conclusion,
HDC rs17740607 polymorphism is at least a partial loss-of-function variant and acts as
a protective factor against CHF, which provides novel highlights for investigating
the contribution of CHF.
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Article Info
Publication History
Published online: March 14, 2015
Accepted:
February 26,
2015
Received in revised form:
February 26,
2015
Received:
December 12,
2014
Footnotes
G-HH, W-KC, and J-RM contributed equally to this work.
This work was supported by Grants 81460560 and 81173643 from the National Natural Science Foundation of China , Grant 2013M532122 from the National Science Foundation for Post-doctoral Scientists of China , Grant 08143047 from the Fundamental Research Funds for the Central Universities of China , and Grants 13QNP063 and 14QNP051 from the PLA Youth Development Project for Medical Science .
See page 1561 for disclosure information.
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