Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Biochemical and Medical Characteristics of the Participants in the Study
2.2. Analysis of the Association between SNPs and T2DM
2.3. Model of Inheritance Analysis
2.4. Association of Haplotypes with T2DM
2.5. Gene-Interaction Network
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. DNA Isolation and Genotyping
4.3. Statistical Analysis
4.4. Bioinformatic Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Case Group n = 201 Mean ± SD | Control Group n = 100 Mean ± SD | p |
---|---|---|---|
Females/males ϯ | 75/126 | 52/48 | n/a |
Age (years) | 56.184 ± 13.65 | 46.540 ± 15.143 | <0.001 * |
Duration of disease (years) | 13.597 ± 5.246 | n/a | n/a |
Weight (kg) | 73.5 ± 13.6 | 66.480 ± 6.790 | <0.001 * |
BMI (kg/m2) | 26.77 ± 4.14 | 23.343 ± 2.171 | <0.001 * |
HTN (%) | 46 | 24 | <0.001 * |
Hb1AC (%) | 8.562 ± 2.27 | 4.871 ± 0.264 | <0.001 * |
FPG (mmol/L) | 8.0 ± 1.7 | 4.63 ± 0.39 | <0.001 * |
Gene | SNP | Allele | Case/Control Frequencies | p | OR (95% CI) | |
---|---|---|---|---|---|---|
CACNA1D | rs312480 | T | 0.03 | 0.08 | 0.006 ϯ | 0.35 (0.14–0.81) |
C | 0.97 | 0.92 | 2.82 (1.22–6.67) | |||
rs9841978 | G | 0.84 | 0.8 | 0.20 | 1.23 (0.77–1.91) | |
A | 0.16 | 0.2 | 0.81 (0.51–1.29) | |||
rs312486 | G | 0.13 | 0.1 | 0.16 | 1.36 (0.77–2.49) | |
C | 0.87 | 0.9 | 0.73 (0.40–1.29) | |||
KCNQ1 | rs2237897 | C | 0.7 | 0.7 | 0.50 | 0.98 (0.66–1.44) |
T | 0.3 | 0.3 | 1.01 (0.69–1.50) | |||
rs2074196 | G | 0.67 | 0.69 | 0.38 | 0.92 (0.63–1.35) | |
T | 0.33 | 0.31 | 1.07 (0.73–1.55) | |||
rs2283228 | A | 0.68 | 0.69 | 0.45 | 0.96 (0.65–1.40) | |
C | 0.32 | 0.31 | 1.03 (0.71–1.52) | |||
rs2237892 | C | 0.7 | 0.7 | 0.45 | 0.96 (0.64–1.41) | |
T | 0.3 | 0.3 | 1.04 (0.70–1.53) | |||
KCNJ11 | rs5218 | G | 0.93 | 0.94 | 0.44 | 0.89 (0.41–1.82) |
A | 0.07 | 0.06 | 1.11 (0.54–2.40) | |||
rs5219 | T | 0.3 | 0.46 | 0.0001 * | 0.50 (0.35–0.73) | |
C | 0.7 | 0.55 | 1.96 (1.35–2.82) | |||
CACNA1E | rs2253388 | T | 0.37 | 0.36 | 0.43 | 1.04 (0.72–1.51) |
C | 0.63 | 0.64 | 0.88 (0.61–1.28) | |||
rs3753737 | G | 0.42 | 0.55 | 0.002 * | 0.59 (0.41–0.85) | |
A | 0.58 | 0.45 | 1.66 (1.16–2.38) | |||
rs175338 | A | 0.34 | 0.24 | 0.005 ϯ | 1.65 (1.11–2.48) | |
G | 0.66 | 0.76 | 0.60 (0.40–0.90) |
Gene | SNP-Genotypes | Case/Control Frequencies | p | OR (95%CI) | ||
---|---|---|---|---|---|---|
CACNA1D | rs312480 | C/T | 0.06 | 0.16 | 0.26 | 0.33 (0.13–0.79) |
C/C | 0.94 | 0.84 | 0.005 ϯ | 3.0 (1.26–7.25) | ||
rs9841978 | G/G | 0.7 | 0.67 | 0.33 | 1.15 (0.66–1.99) | |
G/A | 0.27 | 0.27 | 0.54 | 0.99 (0.56–1.78) | ||
A/A | 0.03 | 0.06 | 0.17 | 0.48 (0.12–1.86) | ||
rs312486 | G/G | 0 | 0.02 | n/a | n/a | |
C/G | 0.26 | 0.16 | 0.03 ϯ | 1.88 (0.98–3.74) | ||
C/C | 0.74 | 0.82 | 0.06 | 0.61 (0.31–1.14) | ||
KCNQ1 | rs2237897 | C/C | 0.51 | 0.49 | 0.40 | 1.09 (0.65–1.81) |
C/T | 0.37 | 0.42 | 0.22 | 0.80 (0.47–1.35) | ||
T/T | 0.12 | 0.09 | 0.28 | 1.37 (0.58–3.49) | ||
rs2074196 | G/G | 0.46 | 0.47 | 0.50 | 0.97 (0.58–1.61) | |
G/T | 0.42 | 0.44 | 0.43 | 0.93 (0.55–1.56) | ||
T/T | 0.12 | 0.09 | 0.33 | 1.30 (0.53–3.34) | ||
rs2283228 | A/A | 0.48 | 0.47 | 0.46 | 1.05 (0.63–1.75) | |
A/C | 0.4 | 0.44 | 0.28 | 0.84 (0.50–1.41) | ||
C/C | 0.12 | 0.09 | 0.28 | 1.37 (0.58–3.49) | ||
rs2237892 | C/C | 0.51 | 0.5 | 0.46 | 1.05 (0.63–1.74) | |
C/T | 0.37 | 0.41 | 0.28 | 0.83 (0.49–1.41) | ||
T/T | 0.12 | 0.09 | 0.28 | 1.37 (0.58–3.49) | ||
KCNJ11 | rs5218 | G/G | 0.87 | 0.87 | 0.53 | 0.96 (0.43–2.04) |
G/A | 0.12 | 0.13 | 0.51 | 0.95 (0.44–2.12) | ||
A/A | 0.01 | 0 | n/a | n/a | ||
rs5219 | T/T | 0.1 | 0.12 | 0.35 | 0.81 (0.35–1.90) | |
C/T | 0.4 | 0.67 | <0.0001 * | 0.35 (0.19–0.55) | ||
C/C | 0.5 | 0.21 | <0.0001 * | 3.79 (2.12–6.96) | ||
CACNA1E | rs2253388 | T/T | 0.12 | 0.09 | 0.24 | 1.43 (0.61–3.64) |
C/T | 0.49 | 0.54 | 0.25 | 0.82 (0.49–1.37) | ||
C/C | 0.38 | 0.37 | 0.46 | 1.05 (0.62–1.79) | ||
rs3753737 | G/G | 0.17 | 0.31 | 0.004 * | 0.45 (0.24–0.82) | |
A/G | 0.51 | 0.48 | 0.37 | 1.11 (0.67–1.85) | ||
A/A | 0.32 | 0.21 | 0.02 ϯ | 1.79 (0.99–3.33) | ||
rs175338 | A/A | 0.12 | 0.03 | 0.004 * | 4.59 (1.34–24.2) | |
G/A | 0.44 | 0.42 | 0.43 | 1.07 (0.64–1.80) | ||
G/G | 0.44 | 0.55 | 0.04 ϯ | 0.63 (0.38–1.06) |
Gene | SNP | Model | p | OR (95% CI) | AIC/BIC | |
---|---|---|---|---|---|---|
CACNA1D | rs9841978 | Codominant | G/G G/A A/A | 0.8 | 1.00 0.85 (0.43–1.71) 1.40 (0.30–6.42) | 29/319 |
Dominant | G/G G/A-A/A | 0.78 | 1.00 0.91 (0.47–1.76) | 295/314 | ||
Recessive | G/G-G/A A/A | 0.62 | 1.00 1.46 (0.32–6.62) | 295/314 | ||
rs312486 | Codominant | C/C C/G G/G | 0.036 ϯ | 1.00 0.41 (0.19–0.89) n/a | 291/313 | |
Dominant | C/C C/G-G/G | 0.03 ϯ | 1.00 0.44 (0.21–0.95) | 291/309 | ||
Recessive | C/C-C/G G/G | n/a | 1.00 n/a | n/a | ||
KCNQ1 | rs2237897 | Codominant | C/C C/T T/T | 0.003 * | 1.00 2.93 (1.52–5.65) 2.56 (0.83–7.89) | 286/308 |
Dominant | C/C C/T-T/T | 0.0007 * | 1.00 2.86 (1.53–5.37) | 284/302 | ||
Recessive | C/C-C/T T/T | 0.44 | 1.00 1.52 (0.53–4.33) | 295/313 | ||
rs2074196 | Codominant | G/G G/T T/T | 0.12 | 1.00 1.79 (0.97–3.32) 2.15 (0.70–6.58) | 293/315 | |
Dominant | G/G G/T-T/T | 0.04 ϯ | 1.00 1.84 (1.01–3.33) | 291/310 | ||
Recessive | G/G-G/T T/T | 0.39 | 1.00 1.60 (0.55–4.63) | 295/313 | ||
rs2283228 | Codominant | A/A C/A C/C | 0.007 ϯ | 1.0 2.65 (1.39–5.05) 2.49 (0.81–7.71) | 288/310 | |
Dominant | A/A C/A-C/C | 0.001 * | 1.00 2.62 (1.41–4.88) | 286/304 | ||
Recessive | A/A-C/A C/C | 0.44 | 1.00 1.52 (0.53–4.33) | 295/313 | ||
rs2237892 | Codominant | C/C C/T T/T | 0.007 ϯ | 1.00 2.67 (1.39–5.12) 2.43 (0.79–7.45) | 287/310 | |
Dominant | C/C C/T-T/T | 0.001 * | 1.00 2.63 (1.41–7.45) | 286/310 | ||
Recessive | C/C-C/T T/T | 0.44 | 1.00 1.52 (0.53–4.33) | 295/313 | ||
KCNJ11 | rs5218 | Codominant | G/GG/A A/A | 0.39 | 1.00 0.95 (0.42–2.18) n/a | 295/318 |
Dominant | G/G G/A-A/A | 0.72 | 1.00 0.86 (0.38–1.94) | 295/314 | ||
Recessive | G/G-G/A A/A | 0.17 | 1.00 n/a | 293/314 | ||
rs5219 | Codominant | C/C T/C T/T | 0.16 | 1.00 1.68 (0.84–3.36) 2.34 (0.88–6.26) | 294/316 | |
Dominant | C/C T/C-T/T | 0.07 | 1.0 1.81 (0.94–3.49) | 292/311 | ||
Recessive | C/C-T/C T/T | 0.23 | 1.00 1.75 (0.71–4.32) | 294/312 | ||
CACNA1E | rs2253388 | Codominant | C/C C/T T/T | 0.18 | 1.00 0.76(0.40–1.43) 0.4 (0.15–1.09) | 294/316 |
Dominant | C/C C/T-T/T | 0.21 | 1.00 0.68 (0.37–1.25) | 294/312 | ||
Recessive | C/C-C/T T/T | 0.10 | 1.00 0.48 (0.19–1.19) | 293/311 | ||
rs3753737 | Codominant | A/A G/A G/G | 0.29 | 1.00 1.53 (0.75–3.12) 1.84 (0.83–4.07) | 295/317 | |
Dominant | A/A G/A-G/G | 0.14 | 1.0 1.64 (0.84–3.18) | 293/312 | ||
Recessive | A/A-G/A G/G | 0.3 | 1.00 1.40 (0.74–2.66) | 294/313 | ||
rs175338 | Codominant | G/G G/A A/A | <0.0001 * | 1.00 0.62 (0.33–1.17) 0.08 (0.02–0.31) | 279/301 | |
Dominant | G/G G/A-A/A | 0.009 ϯ | 1.00 0.46 (0.25–0.83) | 289/307 | ||
Recessive | G/G-G/A A/A | <0.0001 * | 1.00 0.09 (0.02–0.38) | 279/298 |
Gene | Haplotype | Frequency | p | OR (95% CI) |
---|---|---|---|---|
CACNA1D | CGC | 0.755 | --- | 1.00 |
CAC | 0.085 | <0.0001 * | 48.69 (12.14–195.25) | |
CAG | 0.073 | <0.0001 * | 0.00 (0.00–0.02) | |
CGG | 0.0389 | 0.000004 * | 40.77 (5.00–332.33) | |
KCNQ1 | CGAC | 0.6727 | --- | 1.00 |
TTCT | 0.294 | 0.015 ϯ | 1.85 (1.13–3.04) | |
CTCC | 0.013 | 0.7 | 0.71 (0.12–4.12) | |
CTAC | 0.011 | 1.00 | n/a | |
KCNJ11 | GC | 0.579 | --- | 1.00 |
GT | 0.350 | 0.073 | 1.55 (0.96–2.49) | |
AC | 0.069 | 0.82 | 0.91 (0.42–1.99) | |
CACNA1E | CAG | 0.394 | --- | 1.00 |
CGG | 0.211 | 0.38 | 1.28 (0.74–2.23) | |
TGA | 0.176 | 0.19 | 0.62 (0.30–1.27) | |
TAA | 0.106 | 0.08 | 0.42 (0.16–1.12) | |
TGG | 0.062 | 0.0002 * | 7.14 (2.55–19.98) | |
TAG | 0.022 | 0.15 | 3.41 (0.64–18.27) | |
CGA | 0.015 | 0.023 ϯ | 13.36 (1.45–123.23) | |
CAA | 0.011 | 0.54 | 2.33 (0.16–34.32) |
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Díaz-García, J.D.; Leyva-Leyva, M.; Sánchez-Aguillón, F.; de León-Bautista, M.P.; Fuentes-Venegas, A.; Torres-Viloria, A.; Tenorio-Aguirre, E.K.; Morales-Lázaro, S.L.; Olivo-Díaz, A.; González-Ramírez, R. Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2024, 25, 9196. https://doi.org/10.3390/ijms25179196
Díaz-García JD, Leyva-Leyva M, Sánchez-Aguillón F, de León-Bautista MP, Fuentes-Venegas A, Torres-Viloria A, Tenorio-Aguirre EK, Morales-Lázaro SL, Olivo-Díaz A, González-Ramírez R. Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2024; 25(17):9196. https://doi.org/10.3390/ijms25179196
Chicago/Turabian StyleDíaz-García, Juan Daniel, Margarita Leyva-Leyva, Fabiola Sánchez-Aguillón, Mercedes Piedad de León-Bautista, Abel Fuentes-Venegas, Alfredo Torres-Viloria, Erika Karina Tenorio-Aguirre, Sara Luz Morales-Lázaro, Angélica Olivo-Díaz, and Ricardo González-Ramírez. 2024. "Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 25, no. 17: 9196. https://doi.org/10.3390/ijms25179196