KCNQ1 Haplotypes Associate with Type 2 Diabetes in Malaysian Chinese Subjects
Abstract
:1. Introduction
2. Results
2.1. Association of KCNQ1 SNPs with T2D
2.2. Association of KCNQ1 Haplotypes and Diplotypes with T2D
2.3. Impact of KCNQ1 SNPs, Haplotypes and Diplotypes on Beta-Cell Function in Normal Subjects
3. Discussion
4. Materials and Methods
4.1. Subjects and Data Collection
4.2. Biochemical Analyses
4.3. Genetic Analyses
4.4. Statistical Analysis
5. Conclusions
Acknowledgments
- Conflict of InterestThe authors declare no conflict of interest.
References
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Parameters | Normal n = 230 | Type 2 diabetes n = 300 | P-value | |
---|---|---|---|---|
Gender | Male % | 61.3 | 51 | |
Female % | 38.7 | 49 | ||
Family history of diabetes % | Male % | 32 | 76 | |
Female % | 34 | 63 | ||
Age (years) | 52.9 ± 9.15 | 49.8 ± 7.42 | <0.001 | |
Height (m) | 1.62 ± 0.08 | 1.63 ± 0.09 | 0.18 | |
Weight (kg) | 63.1 ± 15.5 | 75.0 ± 15.2 | <0.001 | |
BMI(kg/m2) | 24.1 ± 5.14 | 28.3 ± 5.15 | <0.001 | |
Waist (cm) | 84.7 ± 13.1 | 95.7 ± 12.3 | <0.001 | |
Hip (cm) | 99 ± 10.1 | 104 ± 10.1 | 0.001 | |
Waist/Hip | 0.85 ± 0.07 | 0.92 ± 0.07 | <0.001 | |
Systolic blood pressure | 136 ± 18.5 | 136 ± 18.5 | 0.97 | |
81 ± 9.7 | 82 ± 10.5 | 0.20 | ||
Fasting insulin (pmol/L) | 63.8 ± 44.6 | 103 ± 56.6 | <0.001 | |
Fasting glucose (mmol/L) | 5.1 ± 0.49 | 8.3 ± 2.74 | <0.001 | |
Triacylglycerol (mmol/L) | 1.1 ± 0.44 | 2.1 ± 1.20 | <0.001 | |
HDL cholesterol (mmol/L) | 1.52 ± 0.32 | 1.21 ± 0.28 | <0.001 | |
Insulin resistance (IR) | 1.4 ± 0.93 | 2.5 ± 1.44 | <0.001 |
Recessive model | Dominant model | Additive model | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
NPs | Group | Genotype n (distribution %) | OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | ||
First logistic regression model, analysis adjusted for age and gender
| ||||||||||
rs2237892 | TT | CT | CC | 1.9 (1.29–2.66) | 0.001 | 2.1 (1.09–3.94) | 0.026 | 1.6 (1.25–2.18) | 0.0005 | |
normal | 27(11.7) | 90(39.1) | 113(49.1) | |||||||
diabetic | 18(6.0) | 99(33.0) | 183(61.0) | |||||||
rs2283228 | CC | AC | AA | 1.8 (1.24–2.52) | 0.002 | 1.7 (0.97–2.93) | 0.06 | 1.5 (1.17–1.97) | 0.002 | |
normal | 33(14.3) | 98(42.6) | 99(43.0) | |||||||
diabetic | 27(9.0) | 105(35.0) | 168(56.0) | |||||||
rs2237895 | CC | AC | AA | 1.6 (0.83–3.17) | 0.16 | 1.7 (1.17–2.39) | 0.004 | 1.5 (1.14–2.01) | 0.004 | |
normal | 14(6.1) | 96(41.7) | 120(52.2) | |||||||
diabetic | 30(10.0) | 147(49.0) | 123(41.0) | |||||||
Second logistic regression model, analysis adjusted for age, gender, and body mass index
| ||||||||||
rs2237892 * | TT | CT | CC | 2.2 (1.5–3.4) | 0.0002 | 2.7 (1.3–5.5) | 0.007 | 2.0 (1.4–2.7) | 5.1 × 10−5 | |
normal | 27(12.6) | 81(37.7) | 107(49.8) | |||||||
diabetic | 18(6.0) | 99(33.0 | 183(61.0) | |||||||
rs2283228 * | CC | AC | AA | 2.3 (1.5–3.5) | 7.3 × 10−5 | 2.2 (1.2–4.1) | 0.011 | 1.9 (1.4–2.5) | 5.2 × 10−5 | |
normal | 33(14.9) | 89(40.3) | 99(44.8) | |||||||
diabetic | 27(9.0) | 105(35.0) | 168(56.0) | |||||||
rs2237895 * | CC | AC | AA | 3.7 (1.7–8.1) | 0.001 | 2.0 (1.3–3.0) | 0.001 | 1.9 (1.4–2.7) | 7.8 × 10−5 | |
normal | 11(5.0) | 96(44.0) | 111(50.9) | |||||||
diabetic | 30(10.0) | 147(49.0) | 123(41.0) |
Haplotypes rs2237892, rs2283228, rs2237895 | Frequency
| |||||
---|---|---|---|---|---|---|
Normal n (230) | Type 2 diabetes n (300) | Odds ratio | 95% CI | P-Value | Overall P-value | |
First logistic regression model, analysis adjusted for age and gender
| ||||||
CAC | 0.44 | 0.51 | 1.4 | 0.99–2.01 | 0.057 | 7.49 × 10−6 a |
TCA | 0.33 | 0.15 | 0.33 | 0.21–0.51 | 8.4 × 10−7 | |
CAA | 0.13 | 0.16 | 1.3 | 0.86–2.21 | 0.263 | |
CCA | 0.05 | 0.04 | 0.7 | 0.30–1.63 | 0.41 | |
TAA | 0.01 | 0.06 | 4.6 | 1.31–16.19 | 0.017 | |
CCC | 0.02 | 0.07 | 3.2 | 1.20–8.81 | 0.021 | |
Second logistic regression model, analysis adjusted for age, gender and body mass index
| ||||||
CAC * | 0.44 | 0.51 | 1.7 | 1.1–2.4 | 0.008 | |
TCA * | 0.34 | 0.15 | 0.17 | 0.1–0.28 | 3.7 × 10−11 | |
CAA * | 0.14 | 0.16 | 1.4 | 0.79–2.4 | 0.26 | |
CCA * | 0.05 | 0.04 | 0.54 | 0.2–1.5 | 0.23 | |
TAA * | 0.01 | 0.06 | 6.0 | 1.6–22.1 | 0.007 | |
CCC * | 0.02 | 0.07 | 2.6 | 0.88–7.5 | 0.083 |
Diplotypes rs2237892, rs2283228, rs2237895 | (Frequency)
| |||||
---|---|---|---|---|---|---|
Normal n (230) | Type 2 diabetes n (300) | Odds ratio | 95% CI | P-Value | Overall P-value | |
First logistic regression model, analysis adjusted for age and gender
| ||||||
CAA-CAC | 0.22 | 0.25 | 1.3 | 0.86–1.99 | 0.21 | 8.1 × 10−7 a |
CAA-CAA | 0.13 | 0.16 | 1.3 | 0.81–2.21 | 0.26 | |
CAA-TCA | 0.18 | 0.09 | 0.4 | 0.21–0.63 | 0.0003 | |
TCA-CAC | 0.13 | 0.12 | 0.92 | 0.54–1.57 | 0.77 | |
TCA-TCA | 0.12 | 0.02 | 0.16 | 0.06–0.40 | 8 × 10−5 | |
CAC-CAC | 0.03 | 0.06 | 2.2 | 0.85–5.74 | 0.104 | |
CAA-CCA | 0.05 | 0.03 | 0.48 | 0.19–1.19 | 0.11 | |
CCA-CAC | 0.04 | 0.06 | 1.8 | 0.78–4.10 | 0.17 | |
Second logistic regression model, analysis adjusted for age, gender, and body mass index
| ||||||
CAA-CAC * | 0.23 | 0.25 | 1.4 | 0.79–2.4 | 0.26 | |
CAA-CAA * | 0.14 | 0.16 | 1.3 | 0.82–1.3 | 0.26 | |
CAA-TCA * | 0.19 | 0.08 | 0.09 | 0.04–0.18 | 2.9 × 10−10 | |
TCA-CAC * | 0.14 | 0.12 | 1.0 | 0.54–1.7 | 0.88 | |
TCA-TCA * | 0.12 | 0.02 | 0.13 | 0.05–0.34 | 4.4 × 10−5 | |
CAC-CAC * | 0.01 | 0.06 | 3.9 | 1.4–10.9 | 0.008 | |
CAA-CCA * | 0.05 | 0.03 | 0.38 | 0.12–1.2 | 0.09 | |
CCA-CAC * | 0.03 | 0.06 | 2.6 | 0.92–7.5 | 0.07 |
Non adjusted HOMA-B means(CI) | Adjusted for age, gender | Adjusted for age, gender, BMI | |||||
---|---|---|---|---|---|---|---|
HOMA-B mean(CI) | Parameter estimate P-value | Univariate P-value | HOMA-B Mean(CI) | Parameter estimate P-value | Univariate P-value | ||
rs2237892 | |||||||
CC(n = 113) | 96(90–103) | 98(92–105) | 0.006 | 0.002 | 100(95–106) | 0.01 | 0.0002 |
CT(n = 90) | 94(87–101) | 92(85–98) | 0.0004 | 90(85–96) | 0.0003 | ||
TT(n = 27) Ref | 120(104–137) | 121(106–138) | 118(105–132) | ||||
rs2283228 | |||||||
AA(99) | 97(90–104) | 97(90–104) | 0.33 | 0.584 | 102(96–109) | 0.80 | 0.034 |
AC(98) | 97(87–101) | 97(90–103) | 0.30 | 92(86–97) | 0.039 | ||
CC(33) Ref | 104(92–118) | 104(92–118) | 104(94–115) | ||||
rs2237895 | |||||||
CC(14) | 100(83–122) | 98(81–119) | 0.91 | 0.74 | 106(90–125) | 0.36 | 0.554 |
AC(96) | 95(88–102) | 96(89–103) | 0.44 | 96(91–103) | 0.70 | ||
AA(120) Ref | 100(94–107) | 99(93–106) | 98(93–104) | ||||
haplotypes | |||||||
CAA(n = 30) | 84(74–95) | 85(75–97) | 0.001 | 0.003 | 90(81–100) | 0.007 | 0.014 |
CAC(n = 102) | 97(91–104) | 97(91–104) | 0.026 | 97(92–103) | 0.026 | ||
TCA(n = 75) Ref | 111(103–120) | 110(102–119) | 107(101–115) | ||||
Diplotype | |||||||
CAA-CAA(n = 30) | 84(75–94) | 85(76–95) | 4.0 × 10−5 | 1.5 × 10−6 | 90(81–99) | 0.0001 | 5.7 × 10−6 |
CAA-CAC(n = 51) | 106(97–115) | 107(98–116) | 0.12 | 110(102–119) | 0.20 | ||
CAA-TCA(n = 42) | 117(107–129) | 114(104–126) | 0.55 | 105(96–115) | 0.062 | ||
TCA-CAC(n = 30) | 83(75–93) | 84(75–94) | 1.9 × 10−5 | 85(77–94) | 5.8 × 10−6 | ||
TCA-TCA(n = 27) Ref | 120(106–134) | 120(107–135) | 120(108–133) |
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Saif-Ali, R.; Ismail, I.S.; Al-Hamodi, Z.; Al-Mekhlafi, H.M.; Siang, L.C.; Alabsi, A.M.; Muniandy, S. KCNQ1 Haplotypes Associate with Type 2 Diabetes in Malaysian Chinese Subjects. Int. J. Mol. Sci. 2011, 12, 5705-5718. https://doi.org/10.3390/ijms12095705
Saif-Ali R, Ismail IS, Al-Hamodi Z, Al-Mekhlafi HM, Siang LC, Alabsi AM, Muniandy S. KCNQ1 Haplotypes Associate with Type 2 Diabetes in Malaysian Chinese Subjects. International Journal of Molecular Sciences. 2011; 12(9):5705-5718. https://doi.org/10.3390/ijms12095705
Chicago/Turabian StyleSaif-Ali, Riyadh, Ikram S. Ismail, Zaid Al-Hamodi, Hesham M. Al-Mekhlafi, Lee C. Siang, Aied M. Alabsi, and Sekaran Muniandy. 2011. "KCNQ1 Haplotypes Associate with Type 2 Diabetes in Malaysian Chinese Subjects" International Journal of Molecular Sciences 12, no. 9: 5705-5718. https://doi.org/10.3390/ijms12095705