Background: Increasing studies have reported that 5′-nucleotidase cytosolic II (NT5C2) has a strong relationship with coronary heart disease (CHD) development. This study was designed to examine the relationship between NT5C2 polymorphisms and CHD in the Chinese Han population. Methods: We studied 501 CHD patients and 496 healthy controls from the Second Affiliated Hospital of Hainan Medical University in Hainan Province, China. Four single nucleotide polymorphisms (SNPs) in NT5C2 were selected and genotyped using Agena MassARRAY technology. Odds ratios and 95% confidence intervals were calculated using logistic regression after adjusting for age and gender. Stratification analysis was performed by age and gender in all individuals; we especially investigated the effects of NT5C2 SNPs on hypertension and diabetes among CHD patients. Results: rs2148198 of NT5C2 was strongly associated with an increased risk of CHD (allele: p = 0.045; codominant: p = 0.007; additive: p = 0.016). Stratified analysis revealed that rs2148198 was associated with increased CHD risk in individuals aged ≤61 years and males. For CHD patients, rs2148198 significantly affected the risk of hypertension and diabetes (p < 0.05). Further, rs79237883 of NT5C2 was associated with decreased susceptibility to hypertension in multiple genetic models for individuals with CHD (allele: p = 0.007; codominant: p = 0.001; dominant: p = 0.001; additive: p = 0.008). Conclusion: This study reports the association of NT5C2 gene variants and CHD susceptibility in the Chinese Han population. Especially, NT5C2 rs2148198 was significantly associated with CHD risk in the subgroups of males, hypertension, and diabetes.

1.
Mathers
CD
,
Salomon
JA
,
Ezzati
M
,
Begg
S
,
Hoorn
SV
,
Lopez
AD
, et al.
Sensitivity and uncertainty analyses for burden of disease and risk factors estimates
.
2006
.
2.
Zhang
XH
,
Lu
ZL
,
Liu
L
.
Coronary heart disease in China
.
Heart
.
1999
;
94
(
9
):
1126
31
.
3.
Sun
YX
,
Gao
CY
,
Lu
Y
,
Fu
X
,
Jia
JG
,
Zhao
YJ
, et al.
Association between PPAP2B gene polymorphisms and coronary heart disease susceptibility in Chinese Han males and females
.
Oncotarget
.
2017
;
8
(
8
):
13166
73
.
4.
Sergi
SB
,
Carla
LG
,
Gavin
L
,
Roberto
E
.
Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants
.
Appl Clin Genet
.
2014
;
7
:
15
32
.
5.
Poulter
N
.
Coronary heart disease is a multifactorial disease
.
Am J Hypertens
.
1999
;
12
(
10 Pt 2
):
92S
5S
.
6.
Arnett
DK
,
Baird
AE
,
Barkley
RA
,
Basson
CT
,
Boerwinkle
E
,
Ganesh
SK
, et al.
Relevance of genetics and genomics for prevention and treatment of cardiovascular disease: a scientific statement from the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group
.
Circulation
.
2013
;
115
(
22
):
2878
901
.
7.
Marenberg
ME
,
Risch
N
,
Berkman
LF
,
Floderus
B
,
De Faire
U
.
Genetic susceptibility to death from coronary heart disease in a study of twins
.
N Engl J Med
.
1994
;
330
(
15
):
1041
6
.
8.
Wang
F
,
Ji
Y
,
Chen
X
,
Song
Y
,
Huang
S
,
Zhou
C
, et al.
ABCA1 variants rs2230806 (R219K), rs4149313 (M8831I), and rs9282541 (R230C) are associated with susceptibility to coronary heart disease
.
J Clin Lab Anal
.
2019
;
33
(
6
):
e22896
.
9.
Kibos
A
,
Guerchicoff
A
.
Susceptibility genes for coronary heart disease and myocardial infarction
.
Acute Card Care
.
2011
;
13
(
3
):
136
42
.
10.
Tomita
M
,
Mizuno
S
,
Yamanaka
H
,
Hosoda
Y
,
Sakuma
K
,
Matuoka
Y
, et al.
Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers
.
J Epidemiol
.
2000
;
10
(
6
):
403
9
.
11.
Reunanen
A
,
Takkunen
H
,
Knekt
P
,
Aromaa
A
.
Hyperuricemia as a risk factor for cardiovascular mortality
.
Acta Med Scand Suppl
.
2010
;
668
(
S668
):
49
59
.
12.
Levine
W
,
Dyer
AR
,
Shekelle
RB
,
Schoenberger
JA
,
Stamler
J
.
Serum uric acid and 11.5-year mortality of middle-aged women: findings of the Chicago Heart Association Detection Project in Industry
.
J Clin Epidemiol
.
1989
;
42
(
3
):
257
67
.
13.
Oh
HR
,
Choi
YJ
,
Yoo
NJ
,
Lee
SH
.
Leukemia relapse-associated mutation of NT5C2 gene is rare in de Novo acute leukemias and solid tumors
.
Pathol Oncol Res
.
2016
;
22
(
1
):
223
4
.
14.
Ipata
PL
,
Tozzi
MG
.
Recent advances in structure and function of cytosolic IMP-GMP specific 5′-nucleotidase II (cN-II)
.
Purinergic Signal
.
2006
;
2
(
4
):
669
75
.
15.
Hnízda
A
,
Fábry
M
,
Moriyama
T
,
Pachl
P
,
Kugler
M
,
Brinsa
V
, et al.
Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation
.
Leukemia
.
2018
;
32
(
6
):
1393
403
.
16.
Pesi
R
,
Petrotto
E
,
Colombaioni
L
,
Allegrini
S
,
Garcia-Gil
M
,
Camici
M
, et al.
Cytosolic 5′-nucleotidase II silencing in a human lung carcinoma cell line opposes cancer phenotype with a concomitant increase in p53 phosphorylation
.
Int J Mol Sci
.
2018
;
19
(
7
):
2115
.
17.
Straussberg
R
,
Onoufriadis
A
,
Konen
O
,
Zouabi
Y
,
Cohen
L
,
Lee
JYW
, et al.
Novel homozygous missense mutation in NT5C2 underlying hereditary spastic paraplegia SPG45
.
Am J Med Genet A
.
2017
;
173
(
11
):
3109
13
.
18.
Jordheim
LP
.
Expanding the clinical relevance of the 5′-nucleotidase cN-II/NT5C2
.
Purinergic Signal
.
2018
;
14
(
4
):
321
9
.
19.
Dichgans
M
,
Malik
R
,
König
IR
,
Rosand
J
,
Clarke
R
,
Gretarsdottir
S
, et al.
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants
.
Stroke
.
2014
;
45
(
1
):
24
36
.
20.
López-Mejías
R
,
Corrales
A
,
Vicente
E
,
Robustillo-Villarino
M
,
González-Juanatey
C
,
Llorca
J
, et al.
Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis
.
Sci Rep
.
2017
;
7
:
40303
.
21.
Sirotina
S
,
Ponomarenko
I
,
Kharchenko
A
,
Bykanova
M
,
Bocharova
A
,
Vagaytseva
K
, et al.
A novel polymorphism in the promoter of the CYP4A11 gene is associated with susceptibility to coronary artery disease
.
Dis Markers
.
2018
;
2018
(
4
):
5812802
12
.
22.
Polonikov
A
,
Kharchenko
A
,
Bykanova
M
,
Sirotina
S
,
Ponomarenko
I
,
Bocharova
A
, et al.
Polymorphisms of CYP2C8, CYP2C9, and CYP2C19 and risk of coronary heart disease in Russian population
.
Gene
.
2017
;
627
:
451
9
.
23.
Xue
W
,
Liu
Y
,
Zhao
J
,
Cai
L
,
Li
X
,
Feng
W
.
Activation of HIF-1 by metallothionein contributes to cardiac protection in the diabetic heart
.
Am J Physiol Heart Circ Physiol
.
2012
;
302
(
12
):
H2528
35
.
24.
Song
C
,
Liu
B
,
Yang
D
,
Diao
H
,
Zhao
L
,
Lu
Y
, et al.
Association between Interleukin-6 gene -572G>C polymorphism and coronary heart disease
.
Cell Biochem Biophys
.
2015
;
71
(
1
):
359
65
.
25.
Jia
Z
,
Zhang
Z
,
Yang
Q
,
Deng
C
,
Li
D
,
Ren
L
.
Effect of IL2RA and IL2RB gene polymorphisms on lung cancer risk
.
Int Immunopharmacol
.
2019
;
74
:
105716
.
26.
Lu
S
,
Zhong
J
,
Zhang
Y
,
Huang
K
,
Wu
M
,
Zhou
Y
, et al.
CYP17A1 polymorphisms are linked to the risk of coronary heart disease in a case-control study
.
J Cardiovasc Pharmacol
.
2019
;
74
(
2
):
98
104
.
27.
Kleber
ME
,
Delgado
G
,
Grammer
TB
,
Silbernagel
G
,
Huang
J
,
Krämer
BK
, et al.
Uric acid and cardiovascular events: a Mendelian Randomization Study
.
J Am Soc Nephrol
.
2015
;
26
(
11
):
2831
8
.
28.
Silbernagel
G
,
Hoffmann
MM
,
Grammer
TB
,
Boehm
BO
,
März
W
.
Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography
.
Nutr Metab Cardiovasc Dis Nmcd
.
2013
;
23
(
1
):
46
52
.
29.
Purnima
S
,
El-Aal
BG
.
Serum uric acid as prognostic marker of coronary heart disease (CHD)
.
Clin Investig Arterioscler
.
2016
;
28
(
5
):
216
24
.
30.
Duarte
RRR
,
Troakes
C
,
Nolan
M
,
Srivastava
DP
,
Murray
RM
,
Bray
NJ
.
Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain
.
Am J Med Genet B Neuropsychiatr Genet
.
2016
;
171
(
6
):
806
14
.
31.
Fthenakis
GC
,
Karagiannidis
A
.
Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women
.
J Hum Genet
.
2011
;
57
(
1
):
46
51
.
32.
Duarte
RRR
,
Bachtel
ND
,
Côtel
MC
,
Lee
SH
,
Selvackadunco
S
,
Watson
IA
, et al.
The psychiatric risk gene NT5C2 regulates adenosine monophosphate-activated protein kinase signaling and protein translation in human neural progenitor cells
.
Biol Psychiatry
,
2019
;
86
(
2
):
120
30
.
33.
Stehouwer
CD
,
Henry
RM
,
Ferreira
I
.
Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease
.
Diabetologia
.
2008
;
51
(
4
):
527
39
.
34.
Zhao
XC
,
Yang
SH
,
Yan
YQ
,
Zhang
X
,
Zhang
L
,
Jiao
B
, et al.
Identification of differential gene expression profile from peripheral blood cells of military pilots with hypertension by RNA sequencing analysis
.
BMC Med Genomics
.
2018
;
11
(
1
):
59
.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.