Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Basic Data Collection and Dyslipidemia Diagnosis
2.3. DNA Extraction
2.4. PCR Amplification
2.5. PCR Products Purification
2.6. Single-Base Extension
2.7. Genotyping Analysis
2.8. Statistical Analysis
3. Results
3.1. Assessment of General Data and Clinical Biochemical Indices
Clinical and Biochemical Indices | Group | χ2/t | p Value | |
---|---|---|---|---|
Normal Control | Dyslipidemia | |||
n (Male/Female) | 764 (375/389) | 712 (354/358) | 0.060 | 0.807 |
Age (year) | 43.60 ± 15.32 | 45.16 ± 15.08 | −1.955 | 0.051 |
Height (cm) | 161.04 ± 8.78 | 162.17 ± 9.06 | −2.408 | 0.016 * |
Weight (kg) | 58.68 ± 10.99 | 67.05 ± 13.87 | −12.813 | <0.001 * |
BMI (kg/m2) | 22.55 ± 3.48 | 25.38 ± 4.20 | −14.040 | <0.001 * |
WC (cm) | 81.23 ± 9.97 | 89.99 ± 11.90 | −15.264 | <0.001 * |
HC (cm) | 93.84 ± 7.60 | 98.62 ± 8.49 | −11.330 | <0.001 * |
WHR | 0.87 ± 0.07 | 0.91 ± 0.08 | −12.068 | <0.001 * |
SBP (mmHg) | 128.68 ± 23.11 | 134.11 ± 24.08 | −4.399 | <0.001 * |
DBP (mmHg) | 80.87 ± 13.76 | 84.30 ± 14.55 | −4.634 | <0.001 * |
TG (mmol/L) | 0.80 ± 0.28 | 2.16 ± 1.74 | −21.397 | <0.001 * |
TC (mmol/L) | 4.00 ± 0.71 | 4.90 ± 1.58 | −14.261 | <0.001 * |
LDL-C (mmol/L) | 2.02 ± 0.52 | 2.73 ± 1.07 | −16.448 | <0.001 * |
HDL-C (mmol/L) | 1.45 ± 0.29 | 1.09 ± 0.43 | 19.517 | <0.001 * |
FPG (mmol/L) | 4.54 ± 1.28 | 4.80 ± 1.73 | −3.300 | 0.001 * |
LPa (mg/L) | 259.51 ± 321.85 | 251.37 ± 348.31 | 0.439 | 0.661 |
ApoA (g/L) | 1.38 ± 0.23 | 1.23 ± 0.37 | 9.104 | <0.001 * |
ApoB (g/L) | 0.73 ± 0.23 | 1.02 ± 0.41 | −16.500 | <0.001 * |
ApoB/ApoA | 0.53 ± 0.17 | 0.85 ± 0.52 | −15.068 | <0.001 * |
Smoking (Yes/No) | (205/557) | (215/489) | 2.368 | 0.124 |
Drinking (Yes/No) | (70/693) | (64/639) | 0.002 | 0.963 |
Family history (Yes/No) | (219/545) | (249/463) | 6.770 | 0.009 * |
3.2. Hardy-Weinberg Equilibrium Testing of and Success Rate of Gene Frequencies
3.3. Association of CETP Snps in Dyslipidemia and Normal Control Individuals in Xinjiang National Minorities
SNP | Chr | Gene | M/m | Group(s) | Genotype Distribution n (%) | Allelic Distribution n (%) | χ2 | p b | OR | 95% CI for OR | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
R/R a | C/R a | C/C a | R a | C a | ||||||||||||||
rs5882 | 16 | CETP | A/G | Dyslipidemia | 99 | (14.0) | 310 | (43.8) | 299 | (42.2) | 508 | (35.9) | 908 | (64.1) | ||||
Normal Control | 111 | (14.7) | 340 | (44.9) | 306 | (40.4) | 562 | (37.1) | 952 | (62.9) | 0.469 | 0.494 | 0.950 | 0.820–1.101 | ||||
rs289714 | 16 | CETP | T/C | Dyslipidemia | 46 | (6.5) | 275 | (38.8) | 387 | (54.7) | 367 | (25.9) | 1049 | (74.1) | ||||
Normal Control | 35 | (4.6) | 286 | (37.8) | 436 | (57.6) | 356 | (23.5) | 1158 | (76.5) | 2.343 | 0.126 | 1.143 | 0.963–1.356 | ||||
rs708272 | 16 | CETP | C/T | Dyslipidemia | 156 | (22.0) | 322 | (45.4) | 231 | (32.6) | 634 | (44.7) | 784 | (55.3) | ||||
Normal Control | 186 | (24.6) | 362 | (47.8) | 209 | (27.6) | 734 | (48.5) | 780 | (51.5) | 3.928 | 0.047 | 0.867 | 0.753–0.998 | ||||
rs711752 | 16 | CETP | G/A | Dyslipidemia | 156 | (22.0) | 323 | (45.6) | 230 | (32.4) | 635 | (44.8) | 783 | (55.2) | ||||
Normal Control | 186 | (24.6) | 362 | (47.8) | 209 | (27.6) | 734 | (48.5) | 780 | (51.5) | 3.787 | 0.045 | 0.861 | 0.745–0.996 | ||||
rs1800775 | 16 | CETP | A/C | Dyslipidemia | 152 | (21.5) | 318 | (45.0) | 236 | (33.4) | 622 | (44.1) | 790 | (55.9) | ||||
Normal Control | 132 | (17.5) | 343 | (45.4) | 281 | (37.2) | 607 | (40.1) | 905 | (59.9) | 4.255 | 0.039 | 1.161 | 1.007–1.339 | ||||
rs1801706 | 16 | CETP | G/A | Dyslipidemia | 5 | (0.7) | 133 | (18.7) | 572 | (80.6) | 143 | (10.1) | 1277 | (89.9) | ||||
Normal Control | 9 | (1.2) | 151 | (19.9) | 597 | (78.9) | 169 | (11.2) | 1345 | (88.8) | 0.752 | 0.386 | 0.900 | 0.709–1.142 | ||||
rs3764261 | 16 | CETP | G/T | Dyslipidemia | 51 | (7.2) | 264 | (37.2) | 394 | (55.6) | 366 | (25.8) | 1052 | (74.2) | ||||
Normal Control | 72 | (9.5) | 334 | (44.1) | 351 | (46.4) | 478 | (31.6) | 1036 | (68.4) | 11.718 | 0.001 | 0.754 | 0.642–0.886 | ||||
rs12149545 | 16 | CETP | G/A | Dyslipidemia | 50 | (7.1) | 251 | (35.4) | 408 | (57.5) | 351 | (24.8) | 1067 | (75.2) | ||||
Normal Control | 68 | (9.0) | 329 | (43.5) | 360 | (47.6) | 465 | (30.7) | 1049 | (69.3) | 12.665 | 0.0003 | 0.744 | 0.633–0.876 |
3.4. SNPs Associated with TG, TC, LDL-C and HDL-C
SNP | Group | Genotypes | n | TG | TC | LDL-C | HDL-C |
---|---|---|---|---|---|---|---|
rs708272 | Normal Control | CC | 209 | 0.83 ± 0.31 * | 4.04 ± 0.77 | 2.08 ± 0.55 * | 1.45 ± 0.31 |
CT | 362 | 0.77 ± 0.27 * | 3.99 ± 0.65 | 2.00 ± 0.51 | 1.43 ± 0.28 * | ||
TT | 186 | 0.80 ± 0.28 | 3.96 ± 0.74 | 1.96 ± 0.52 * | 1.51 ± 0.30 * | ||
Dyslipidemia | CC | 231 | 2.24 ± 2.42 | 4.89 ± 1.63 | 2.74 ± 1.09 | 1.07 ± 0.46 | |
CT | 322 | 2.07 ± 1.15 | 4.78 ± 1.54 * | 2.65 ± 1.02 * | 1.07 ± 0.40 | ||
TT | 156 | 2.25 ± 1.57 | 5.15 ± 1.57 * | 2.88 ± 1.12 * | 1.14 ± 0.43 | ||
rs1800775 | Normal Control | AA | 281 | 0.83 ± 0.27 * | 4.01 ± 0.65 | 1.99 ± 0.52 | 1.48 ± 0.30 |
AC | 343 | 0.77 ± 0.28 * | 3.99 ± 0.67 | 2.02 ± 0.52 | 1.44 ± 0.30 | ||
CC | 132 | 0.80 ± 0.31 | 3.96 ± 0.90 | 2.04 ± 0.56 | 1.45 ± 0.26 | ||
Dyslipidemia | AA | 236 | 2.15 ± 1.42 | 5.02 ± 1.59 | 2.80 ± 1.09 | 1.12 ± 0.42 | |
AC | 318 | 2.22 ± 1.95 | 4.88 ± 1.57 | 2.73 ± 1.08 | 1.06 ± 0.38 | ||
CC | 152 | 2.08 ± 1.77 | 4.77 ± 1.57 | 2.63 ± 1.01 | 1.08 ± 0.52 | ||
rs3764261 | Normal Control | GG | 351 | 0.81 ± 0.29 | 4.00 ± 0.73 | 2.05 ± 0.53 | 1.44 ± 0.29 |
GT | 334 | 0.78 ± 0.27 | 3.99 ± 0.67 | 1.98 ± 0.53 | 1.47 ± 0.31 | ||
TT | 72 | 0.83 ± 0.30 | 4.03 ± 0.76 | 2.02 ± 0.49 | 1.46 ± 0.24 | ||
Dyslipidemia | GG | 394 | 2.15 ± 1.97 | 4.82 ± 1.59 * | 2.68 ± 1.05 | 1.08 ± 0.44 | |
GT | 264 | 2.22 ± 1.47 | 4.93 ± 1.59 | 2.75 ± 1.04 | 1.10 ± 0.42 | ||
TT | 51 | 2.04 ± 1.08 | 5.31 ± 1.41 * | 2.99 ± 1.26 | 1.10 ± 0.35 | ||
rs711752 | Normal Control | GG | 209 | 0.83 ± 0.31 * | 4.04 ± 0.77 | 2.08 ± 0.55 * | 1.45 ± 0.31 |
AG | 362 | 0.77 ± 0.27 * | 3.99 ± 0.65 | 2.00 ± 0.51 | 1.43 ± 0.28 * | ||
AA | 186 | 0.80 ± 0.28 | 3.96 ± 0.74 | 1.96 ± 0.52 * | 1.51 ± 0.30 * | ||
Dyslipidemia | GG | 230 | 2.24 ± 2.42 | 4.89 ± 1.63 | 2.74 ± 1.09 | 1.07 ± 0.46 | |
AG | 323 | 2.07 ± 1.15 | 4.78 ± 1.54 * | 2.65 ± 1.02 * | 1.07 ± 0.40 | ||
AA | 156 | 2.25 ± 1.57 | 5.15 ± 1.57 * | 2.88 ± 1.12 * | 1.14 ± 0.43 | ||
rs12149545 | Normal Control | GG | 360 | 0.81 ± 0.29 | 4.00 ± 0.73 | 2.05 ± 0.53 | 1.44 ± 0.29 |
AG | 329 | 0.78 ± 0.27 | 3.99 ± 0.67 | 1.98 ± 0.53 | 1.47 ± 0.31 | ||
AA | 68 | 0.83 ± 0.30 | 4.02 ± 0.77 | 2.01 ± 0.48 | 1.46 ± 0.24 | ||
Dyslipidemia | GG | 408 | 2.18 ± 1.96 | 4.84 ± 1.57 * | 2.69 ± 1.05 * | 1.07 ± 0.44 | |
AG | 251 | 2.17 ± 1.47 | 4.91 ± 1.62 | 2.74 ± 1.05 | 1.10 ± 0.42 | ||
AA | 50 | 2.05 ± 1.09 | 5.33 ± 1.41 * | 3.01 ± 1.26 * | 1.10 ± 0.36 |
3.5. Linkage Disequilibrium (LD) Tests
rs12149545 | rs3764261 | rs1800775 | rs711752 | rs708272 | rs289714 | rs5882 | rs1801706 | |
---|---|---|---|---|---|---|---|---|
rs12149545 | — | 1.000 | 0.930 | 0.977 | 0.975 | 0.744 | 0.116 | 0.376 |
rs3764261 | 0.954 | — | 0.928 | 0.913 | 0.910 | 0.677 | 0.124 | 0.386 |
rs1800775 | 0.241 | 0.252 | — | 0.919 | 0.919 | 0.214 | 0.637 | 0.377 |
rs711752 | 0.421 | 0.385 | 0.537 | — | 1.000 | 0.229 | 0.461 | 0.417 |
rs708272 | 0.419 | 0.383 | 0.536 | 0.999 | — | 0.230 | 0.462 | 0.418 |
rs289714 | 0.070 | 0.061 | 0.021 | 0.015 | 0.015 | — | 0.043 | 0.908 |
rs5882 | 0.009 | 0.011 | 0.169 | 0.139 | 0.140 | 0.000 | — | 0.972 |
rs1801706 | 0.006 | 0.007 | 0.012 | 0.024 | 0.024 | 0.032 | 0.195 | — |
Haplotype | Dyslipidemia (%) | Normal Control (%) | χ2 | Fisher’s p | Pearson’s p | OR (95% CI) |
---|---|---|---|---|---|---|
A/T/A/A/T/C/A/G | 9.27 (0.007) | 24.01 (0.016) | 5.679 | 0.017 | 0.017 | 0.408 (0.190–0.874) |
A/T/A/A/T/T/A/G | 185.76 (0.132) | 231.57 (0.154) | 2.911 | 0.087 | 0.087 | 0.834 (0.676–1.028) |
A/T/A/A/T/T/G/A | 12.67 (0.009) | 30.16 (0.020) | 6.144 | 0.013 | 0.013 | 0.443 (0.229–0.858) |
A/T/A/A/T/T/G/G | 123.60 (0.088) | 143.97 (0.096) | 0.556 | 0.456 | 0.455 | 0.908 (0.705–1.170) |
G/G/A/A/T/C/G/G | 103.20 (0.073) | 91.84 (0.061) | 1.741 | 0.187 | 0.186 | 1.217 (0.909–1.628) |
G/G/A/A/T/T/A/G | 67.86 (0.048) | 51.83 (0.034) | 3.480 | 0.062 | 0.062 | 1.419 (0.981–2.054) |
G/G/A/A/T/T/G/A | 65.20 (0.046) | 79.17 (0.053) | 0.623 | 0.430 | 0.430 | 0.873 (0.624–1.223) |
G/G/A/A/T/T/G/G | 25.71 (0.018) | 30.36 (0.020) | 0.144 | 0.704 | 0.704 | 0.903 (0.531–1.534) |
G/G/A/G/C/C/A/G | 12.52 (0.009) | 16.42 (0.011) | 0.303 | 0.581 | 0.581 | 0.813 (0.388–1.702) |
G/G/A/G/C/C/G/G | 5.36 (0.004) | 15.33 (0.010) | 4.206 | 0.040 | 0.040 | 0.371 (0.138–0.995) |
G/G/A/G/C/T/A/G | 67.63 (0.048) | 79.30 (0.053) | 0.338 | 0.561 | 0.561 | 0.906 (0.649–1.264) |
G/G/A/G/C/T/G/A | 18.04 (0.013) | 9.62 (0.006) | 3.182 | 0.074 | 0.074 | 2.017 (0.919–4.426) |
G/G/A/G/C/T/G/G | 50.09 (0.036) | 59.51 (0.040) | 0.323 | 0.569 | 0.569 | 0.895 (0.610–1.313) |
G/G/C/G/C/C/A/G | 196.39 (0.139) | 167.58 (0.111) | 5.255 | 0.021 | 0.021 | 1.294 (1.038–1.615) |
G/G/C/G/C/T/A/G | 329.51 (0.234) | 352.52 (0.234) | 0.001 | 0.978 | 0.977 | 0.998 (0.839–1.186) |
G/G/C/G/C/T/G/A | 27.00 (0.019) | 32.64 (0.022) | 0.233 | 0.629 | 0.629 | 0.881 (0.526–1.475) |
G/G/C/G/C/T/G/G | 41.67 (0.030) | 16.67 (0.011) | 12.697 | 0.0003 | 0.0003 | 2.723 (1.535–4.829) |
4. Discussion
5. Study Limitations
6. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Guo, S.; Hu, Y.; Ding, Y.; Liu, J.; Zhang, M.; Ma, R.; Guo, H.; Wang, K.; He, J.; Yan, Y.; et al. Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China. Int. J. Environ. Res. Public Health 2015, 12, 15979-15992. https://doi.org/10.3390/ijerph121215036
Guo S, Hu Y, Ding Y, Liu J, Zhang M, Ma R, Guo H, Wang K, He J, Yan Y, et al. Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China. International Journal of Environmental Research and Public Health. 2015; 12(12):15979-15992. https://doi.org/10.3390/ijerph121215036
Chicago/Turabian StyleGuo, Shuxia, Yunhua Hu, Yusong Ding, Jiaming Liu, Mei Zhang, Rulin Ma, Heng Guo, Kui Wang, Jia He, Yizhong Yan, and et al. 2015. "Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China" International Journal of Environmental Research and Public Health 12, no. 12: 15979-15992. https://doi.org/10.3390/ijerph121215036