Interaction of functional NPC1 gene polymorphism with smoking on coronary heart disease.
BACKGROUND
The protein of Niemann-pick type C1 gene (NPC1) is known to facilitate the egress of cholesterol and other lipids from late endosomes and lysosomes to other cellular compartments. This study aims to investigate whether the genetic variation in NPC1 is associated with risk of coronary heart disease (CHD) and to detect whether NPC1 might interact with smoking on the risk of CHD.


METHODS
We performed a case-control study, including 873 patients with coronary heart disease (CHD) and 864 subjects without CHD as control. Polymorphisms of NPC1 gene were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP).


RESULTS
A tag-SNP rs1805081 (+644A > G) in NPC1 was identified. The G allele of the +644 locus showed reduced risk of CHD than wild-type genotype in Chinese population (recessive model GG vs. AG+AA: odds ratio [OR] 0.647, 95% CI 0.428 to 0.980, P = 0.039; additive model GG vs. AG vs. AA: OR 0.847, 95% CI 0.718 to 0.998, P = 0.0471). Moreover in smokers, the G-allele carriers had reduced risk of CHD compared with A-allele carries (OR 0.552, 95% CI 0.311 to 0.979, P = 0.0421).


CONCLUSIONS
The results of the present study suggest that NPC1 variants seem to be contributors to coronary heart disease occurrence in Chinese population. Moreover, in smokers, NPC1 variants seem to confer protection to coronary heart disease.
Ma
Weiwei
W
Department of Cardiology, and Sino-German Laboratory for Molecular Medicine, FuWai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, 100037 Beijing, China.
Xu
Jing
J
Wang
Qianqian
Q
Xin
Ying
Y
Zhang
Lin
L
Zheng
Xinxin
X
Wang
Hu
H
Sun
Kai
K
Hui
Rutai
R
Huang
Xiaohong
X
D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D000077296:Niemann-Pick C1 Protein; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein