[Geographical characteristics of single nucleotide polymorphism of candidate genes associated with coronary artery disease in Chinese Han population].
OBJECTIVE
To investigate the geographical characteristics of single nucleotide polymorphism (SNP) of candidate genes associated with coronary artery disease in Chinese Han population.


METHODS
Study population were Chinese Han nationality recruited from Xi'an, Shiyan and Ningbo districts. Patients with coronary artery disease were defined by coronary angiography with stenosis >or= 50% and control subjects with stenosis < 10%, respectively. The DNA was extracted from peripheral white blood cell by approach comprised proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The SNP of ATP-binding cassette transporter (ABCA1)-G596A, cholesteryl ester transfer protein (CETP)-Taq1B, Lipoprotein lipase (LPL)-Hind III and LPL-Pvu II were genotyped by PCR-RFLPs, and verified by gene sequencing.


RESULTS
A Total of 615 patients undertaken coronary angiography were recruited from cardiac center in Xi'an (220), Ningbo (209) and Shiyan district (186), China (mean age 60 +/- 10 years, 75.9% males). Diabetes mellitus was more prevalent in Xi'an Cohort population than Shiyan and Ningbo cohort (P < 0.01). Plasma total cholesterol, LDL cholesterol and triglyceride levels in Xi'an Cohort population were significantly higher, and HDL-C siginificantly lower than in Shiyan and Ningbo cohort population [HDL-C: (1.17 +/- 0.48) mmol/L vs. (1.25 +/- 0.33) mmol/L and (1.29 +/- 0.44) mmol/L, P < 0.05]. Distribution differences for ABCA1-G596A and CETP-Taq1B genotypes were found in Xi'an Cohort population compared to Ningbo and Shiyan cohorts (for ABCA1, Xi'an: 0.24, 0.53, 0.23 and Shiyan: 0.17, 0.62, 0.21 and Ningbo: 0.34, 0.37, 0.29, for GG, AG, AA, respectively, P < 0.01; and for CETP, Xi'an: 0.29, 0.54, 0.17 and Shiyan: 0.38, 0.40, 0.22 and Ningbo: 0.39, 0.49, 0.12 for B1B1, B1B2, B2B2, respectively, P < 0.01), but not for LPL variants. ABCA1-G596A variant predicted HDL-C [Xi'an: (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.2) mmol/L and (1.4 +/- 0.4) mmol/L, P = 0.01; Shiyan: (1.1 +/- 0.4) mmol/L: (1.2 +/- 0.3) mmol/L and (1.3 +/- 0.4) mmol/L, P = 0.03; Ningbo, (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.4) mmol/L and (1.4 +/- 0.3) mmol/L, across GG, GA to AA genotype, respectively, P = 0.01] and TG levels [Xi'an: (2.4 +/- 1.3) mmol/L, (1.9 +/- 0.9) mmol/L and (1.6 +/- 0.8) mmol/L, P < 0.01; Shiyan: (2.1 +/- 1.0) mmol/L, (1.9 +/- 0.8) mmol/L and (1.8 +/- 0.7) mmol/L, P = 0.03; Ningbo: (1.9 +/- 1.1) mmol/L, (1.8 +/- 0.9) mmol/L and (1.6 +/- 0.7) mmol/L, across GG, GA to AA genotype, P = 0.05] with dose-dependent relationship. LPL-Hind III (+) carriers had higher triglycerides in three cohort population [Xi'an: (2.2 +/- 1.0) mmol/L, (1.8 +/- 0.9) mmol/L, (1.6 +/- 0.7) mmol/L, P = 0.01; Shiyan: (2.1 +/- 0.7) mmol/L, (1.9 +/- 1.0) mmol/L, (1.7 +/- 0.6) mmol/L, P = 0.01; Ningbo: (1.8 +/- 1.0) mmol/L, (1.6 +/- 0.6) mmol/L and (1.4 +/- 0.5) mmol/L, for +/+, +/- and -/- genotypes, respectively, P = 0.001]. SNP of CETP-Taq1B, LPL-Hind III and LPL-Pvu II predicted HDL-C and/or TG levels in different cohort population with different manners. All these SNP were not significantly associated with the development of coronary artery disease (all P > 0.05).


CONCLUSIONS
A geographical heterogeneity of environmental and genetic risk factors related to the development of coronary artery disease exists in Chinese Han population. Irrespective of the different geographical cohort of Chinese Han population, the SNP of candidate genes can partly predict the differences in risk-related plasma HDL-C and/or TG levels rather than angiographic coronary artery disease.
Wang
Sheng-Huang
SH
Department of Cardiology, Zhejiang Provincial Ningbo City Hospital, Ningbo 315010, China.
Cui
Han-Bin
HB
Wang
Dong-Qi
DQ
Chen
Xiao-Min
XM
Zhang
Hong-Kao
HK
Cui
Chang-Cong
CC
Chen
Xin-Yi
XY
Liu
Xin-Hong
XH
Zhang
Zheng
Z
Bai
Feng
F
Jb
Muhlestein
M
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D003324:Coronary Artery Disease / Q000208:ethnology* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D005843:Geography; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008071:Lipoprotein Lipase