Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population
Abstract
:1. Introduction
2. Results
2.1. Clinical Characteristics
2.2. Polymerase Chain Reaction (PCR) Products and Genotypes
2.3. Nucleotide Sequences
2.4. Genotypic and Allelic Frequencies
2.5. Genotypes and the Risk of Coronary Heart Disease (CHD) and Ischemic Stroke (IS)
2.6. Linkage Disequilibrium (LD) Analyses
2.7. Gene-Environment Interactions on the Risk of CHD and IS
2.8. Gene–Gene Interactions on the Risk of CHD and IS
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Biochemical Measurements
4.3. Single Nucleotide Polymorphisms (SNP) Selection and Genotyping
4.4. Deoxyribonucleic Acid (DNA) Sequencing
4.5. Statistical Analyses
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
ABCA1 | Adenosine triphosphate-binding cassette transporter A1 |
Apo | Apolipoprotein |
BMI | Body mass index |
CHD | Coronary heart disease |
DNA | Deoxyribonucleic acid |
GWASes | Genome-wide association studies |
HDL-C | High-density lipoprotein cholesterol |
IS | Ischemic stroke |
LD | Linkage disequilibrium |
LDL-C | Low-density lipoprotein cholesterol |
MAF | Minor allele frequency |
MDR | Multifactor dimensionality reduction |
MRI | Magnetic resonance imaging |
PCR | Polymerase chain reaction |
RFLP | Restriction fragment length polymorphism |
SNPs | Single nucleotide polymorphisms |
TC | Total cholesterol |
TG | Triglyceride |
TOAST | Trial of Org 10172 in Acute Stroke Treatment |
References
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Parameter | Control | CHD | IS | p1 | p2 |
---|---|---|---|---|---|
Number | 541 | 565 | 569 | – | – |
Male, n (%) | 346 (64.0) | 394 (69.7) | 396 (69.6) | 0.051 | 0.053 |
Age, years | 61.39 ± 11.41 | 62.31 ± 10.53 | 62.53 ± 11.92 | 0.079 | 0.051 |
Body mass index, kg/m2 | 22.49 ± 2.90 | 23.98 ± 3.21 | 23.50 ± 3.60 | 0.000 | 0.000 |
Cigarette smoking, n (%) | 217 (40.1) | 244 (43.2) | 258 (45.7) | 0.300 | 0.078 |
Diabetes, n (%) | 19 (3.5) | 129 (22.8) | 305 (53.98) | 0.000 | 0.000 |
Hypertension, n (%) | 123 (22.7) | 282 (49.9) | 326 (57.3) | 0.000 | 0.000 |
Hyperlipidemia, n (%) | 229 (42.3) | 277 (49.0) | 84 (14.9) | 0.025 | 0.000 |
Total cholesterol, mmol/L | 4.84 ± 1.07 | 4.55 ± 1.24 | 4.52 ± 1.16 | 0.002 | 0.000 |
Triglyceride, mmol/L | 1.01 (0.69) | 1.34 (0.93) | 1.36 (0.94) | 0.000 | 0.000 |
HDL-C, mmol/L | 1.85 ± 0.51 | 1.14 ± 0.34 | 1.24 ± 0.41 | 0.000 | 0.000 |
LDL-C, mmol/L | 2.77 ± 0.82 | 2.73 ± 1.04 | 2.67 ± 0.91 | 0.511 | 0.071 |
Apolipoprotein (Apo)A1, g/L | 1.37 ± 0.28 | 1.05 ± 0.55 | 1.05 ± 0.55 | 0.000 | 0.000 |
ApoB, g/L | 0.89 ± 0.21 | 0.90 ± 0.28 | 0.90 ± 0.26 | 0.344 | 0.431 |
ApoA1/ApoB | 1.62 ± 0.55 | 1.40 ± 2.51 | 1.19 ± 0.60 | 0.042 | 0.000 |
SNP/Group | Genotype | Allele | pHWE | ||||
---|---|---|---|---|---|---|---|
N | AA | AB | BB | A | B | ||
rs1333040 (C>T) | |||||||
Control | 541 | 60 (11.1) | 225 (41.6) | 256 (47.3) | 345 (31.9) | 737 (68.1) | 0.322 |
CHD | 565 | 39 (6.9) | 232 (41.1) | 294 (52.0) | 310 (27.4) | 820 (72.6) | 0.457 |
IS | 569 | 55 (9.7) | 247 (43.4) | 267 (46.9) | 357 (31.4) | 781 (68.6) | 0.846 |
pCHD | 0.035 | 0.022 | |||||
pIS | 0.681 | 0.794 | |||||
rs1333042 (A>G) | |||||||
Control | 541 | 67 (12.4) | 219 (40.5) | 227 (42.0) | 353 (32.6) | 729 (67.4) | 0.941 |
CHD | 565 | 43 (7.60) | 227 (40.2) | 255 (59.2) | 313 (27.7) | 817 (72.3) | 0.065 |
IS | 569 | 56 (9.7) | 243 (42.7) | 270 (47.6) | 355 (31.2) | 783 (68.8) | 0.066 |
pCHD | 0.021 | 0.011 | |||||
pIS | 0.376 | 0.470 | |||||
rs4977574 (A>G) | |||||||
Control | 541 | 152 (28.1) | 255 (47.1) | 134 (24.8) | 559 (51.7) | 523 (48.3) | 0.191 |
CHD | 565 | 117 (20.7) | 272 (48.1) | 176 (31.2) | 506 (44.8) | 624 (55.2) | 0.527 |
IS | 569 | 121 (21.3) | 276 (48.5) | 172 (30.2) | 518 (45.5) | 620 (54.5) | 0.599 |
pCHD | 0.006 | 0.001 | |||||
pIS | 0.015 | 0.004 | |||||
rs2066715 (A>G) | |||||||
Control | 541 | 97 (17.9) | 266 (49.2) | 178 (32.9) | 460 (42.5) | 622 (57.5) | 0.891 |
CHD | 565 | 101 (17.9) | 298 (52.7) | 166 (29.4) | 500 (44.2) | 630 (55.8) | 0.101 |
IS | 569 | 116 (20.4) | 279 (49.0) | 174 (30.6) | 627 (55.1) | 511 (44.9) | 0.823 |
pCHD | 0.408 | 0.411 | |||||
pIS | 0.510 | 0.256 | |||||
rs2740483 (C>G) | |||||||
Control | 541 | 31 (5.70) | 183 (33.8) | 327 (60.4) | 245 (22.6) | 837 (77.4) | 0.423 |
CHD | 565 | 17 (2.8) | 175 (31.0) | 373 (66.2) | 209 (18.5) | 921 (81.5) | 0.516 |
IS | 569 | 9 (1.6) | 152 (26.7) | 408 (71.7) | 170 (14.9) | 969 (85.1) | 0.223 |
pCHD | 0.034 | 0.016 | |||||
pIS | 0.000 | 0.000 |
SNP/Model | Ref. Genotype | Effect Genotype | CHD (OR 95% CI) | p | IS (OR 95% CI) | p |
---|---|---|---|---|---|---|
rs1333040 | ||||||
Codominant | CC | CT | 1.74 (1.06–2.86) | 0.030 | 1.06 (0.69–1.65) | 0.781 |
TT | 1.84 (1.13–3.01) | 0.014 | 1.13 (0.72–1.75) | 0.598 | ||
Dominant | CC | CT/TT | 1.79 (1.12–2.88) | 0.016 | 1.09 (0.72–1.66) | 0.677 |
Recessive | CC/CT | TT | 1.17 (0.90–1.52) | 0.244 | 0.97 (0.75–1.25) | 0.798 |
Overdominant | CC/TT | CT | 1.03 (0.79–1.35) | 0.820 | 1.07 (0.83–1.39) | 0.606 |
Log-additive | 1.23 (1.00–1.50) | 0.049 | 1.00 (0.83–1.21) | 0.994 | ||
rs1333042 | ||||||
Codominant | AA | AG | 1.73 (1.06–2.80) | 0.027 | 1.17 (0.76–1.79) | 0.483 |
GG | 1.92 (1.20–3.08) | 0.007 | 1.21 (0.78–1.87) | 0.395 | ||
Dominant | AA | AG/GG | 1.83 (1.16–2.89) | 0.010 | 1.19 (0.79–1.79) | 0.418 |
Recessive | AA/AG | GG | 1.24 (0.95–1.61) | 0.115 | 1.00 (0.78–1.30) | 0.974 |
Overdominant | AA/GG | AG | 1.00 (0.76–1.30) | 0.982 | 1.07 (0.82–1.38) | 0.629 |
Log-additive | 1.27 (1.04–1.56) | 0.018 | 1.04 (0.86–1.26) | 0.689 | ||
rs4977574 | ||||||
Condominat | AA | AG | 1.44 (1.04–2.02) | 0.029 | 1.44 (1.05–1.98) | 0.025 |
GG | 1.64 (1.14–2.37) | 0.008 | 1.63 (1.14–2.33) | 0.007 | ||
Dominant | AA | AG/GG | 1.52 (1.11–2.07) | 0.009 | 1.51 (1.12–2.03) | 0.007 |
Recessive | AA/AG | GG | 1.28 (0.96–1.72) | 0.095 | 1.28 (0.96–1.70) | 0.092 |
Overdominant | AA/GG | AG | 1.11 (0.85–1.45) | 0.446 | 1.11 (0.86–1.43) | 0.427 |
Log-additive | 1.27 (1.06–1.53) | 0.010 | 1.27 (1.06–1.52) | 0.008 | ||
rs2066715 | ||||||
Codominant | GG | AG | 1.00 (0.67–1.48) | 0.994 | 1.10 (0.76–1.59) | 0.623 |
AA | 1.19 (0.88–1.61) | 0.260 | 1.00 (0.75–1.34) | 0.992 | ||
Dominant | GG | AG/AA | 1.14 (0.85–1.51) | 0.382 | 1.03 (0.78–1.35) | 0.849 |
Recessive | GG/AG | AA | 0.90 (0.63–1.27) | 0.537 | 1.00 (0.79–1.52) | 0.580 |
Overdominant | GG/AA | AG | 1.19 (0.91–1.55) | 0.199 | 0.97 (0.75–1.25) | 0.801 |
Log-additive | 1.02 (0.85–1.24) | 0.806 | 1.04 (0.87–1.25) | 0.663 | ||
rs2740483 | ||||||
Codominant | GG | GC | 0.82 (0.61–1.08) | 0.159 | 0.64 (0.48–0.85) | 0.002 |
CC | 0.43 (0.22–0.83) | 0.012 | 0.22 (0.10–0.49) | 0.000 | ||
Dominant | GG | CG/CC | 0.76 (0.58–0.99) | 0.044 | 0.58 (0.44–0.76) | 0.000 |
Recessive | GG/CG | CC | 0.46 (0.24–0.89) | 0.020 | 0.25 (0.11–0.56) | 0.001 |
Overdominant | GG/CC | CG | 0.86 (0.65–1.14) | 0.305 | 0.69 (0.52–0.91) | 0.009 |
Log-additive | 0.74 (0.59–0.94) | 0.011 | 0.58 (0.46–0.73) | 0.000 |
Factor | rs1333042 (pCHD) | rs4977574 (pCHD/pIS) | rs2740483 (pCHD/pIS) |
---|---|---|---|
Sex (male vs. female) | 0.967 | 0.729/0.940 | 0.560/0.128 |
Age (≤60 vs. >60 year) | 0.444 | 0.022/0.216 | 0.213/0.490 |
BMI (≤24 vs. >24 kg/m2) | 0.565 | 0.720/0.824 | 0.198/0.035 |
Smoking (yes vs. no) | 0.099 | 0.882/0.299 | 0.839/0.539 |
Hypertension (yes vs. no) | 0.815 | 0.876/0.990 | 0.837/0.331 |
Diabetes (yes vs. no) | NA | 0.119/NA | 0.192/0.159 |
Hyperlipidemia (yes vs. no) | 0.945 | 0.125/0.430 | 0.797/0.607 |
Model | MDR Analysis | LR Analysis | |||||
---|---|---|---|---|---|---|---|
Traing Bal.Acc | Testing Bal.Acc | CVC | p | Wald | OR (95% CI) | p | |
rs4977574 | 0.538 | 0.518 | 9/10 | 0.377 | – | – | – |
A-B | 0.574 | 0.566 | 10/10 | 0.011 | 15.98 | 1.69 (1.31–2.19) | 0.000 |
A-B-C | 0.601 | 0.536 | 7/10 | 0.054 | 7.52 | 1.16 (1.04–1.73) | 0.006 |
A-B-C-D | 0.637 | 0.601 | 10/10 | 0.001 | 5.97 | 1.08 (1.02–1.14) | 0.015 |
Model | MDR Analysis | LR Analysis | |||||
---|---|---|---|---|---|---|---|
Traing Bal.Acc | Testing Bal.Acc | CVC | p | Wald | OR (95% CI) | p | |
rs2740483 | 0.557 | 0.555 | 10/10 | 0.001 | - | - | - |
A-B | 0.603 | 0.602 | 10/10 | 0.001 | 20.56 | 1.80 (1.40–2.32) | 0.000 |
A-B-C | 0.624 | 0.594 | 8/10 | 0.011 | 13.56 | 1.19 (0.90–1.27) | 0.000 |
A-B-C-rs2740483 | 0.654 | 0.602 | 10/10 | 0.001 | 0.22 | 1.02 (0.94–1.40) | 0.640 |
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
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Cao, X.-L.; Yin, R.-X.; Huang, F.; Wu, J.-Z.; Chen, W.-X. Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population. Int. J. Mol. Sci. 2016, 17, 586. https://doi.org/10.3390/ijms17040586
Cao X-L, Yin R-X, Huang F, Wu J-Z, Chen W-X. Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population. International Journal of Molecular Sciences. 2016; 17(4):586. https://doi.org/10.3390/ijms17040586
Chicago/Turabian StyleCao, Xiao-Li, Rui-Xing Yin, Feng Huang, Jin-Zhen Wu, and Wu-Xian Chen. 2016. "Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population" International Journal of Molecular Sciences 17, no. 4: 586. https://doi.org/10.3390/ijms17040586