Genetic association of solute carrier transporter gene variants with metformin response
, , , , , , oraz | 27 lip 2021
O artykule
Article Category: Original Article
Data publikacji: 27 lip 2021
Zakres stron: 47 - 56
DOI: https://doi.org/10.2478/bjmg-2021-0004
Słowa kluczowe
© 2021 Abrahams-October Z, Xhakaza L, Pearce B, Mandisa Masilela C, Benjeddou M, Vincent Adeniyi O, Johnson R, Jebio Ongole J, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Single nucleotide polymorphism information and Hardy-Weinberg p values in the study population.
| SNP | Gene/ Closest Gene | Chromosomal Position | Location | Allele Change | Amino Acid Change | HWE |
|---|---|---|---|---|---|---|
| rs10783050 | 1:96571527 | intergenic | T>C | – | 0.932 | |
| rs1143623 | 2:112838252 | intergenic | C>G | – | 0.309 | |
| rs13266634 | 8:117172544 | missense | C>A/T | Arg325Trp | 0.532 | |
| rs13376631 | 1:171266603 | intron | A>G | – | 0.903 | |
| rs1801282 | 3:12351626 | missense | C>G | Pro12Ala | monomorphic | |
| rs249429 | 5:40782137 | intron | C>T | – | 0.299 | |
| rs2815752 | 1:72346757 | intergenic | G>A | – | 0.636 | |
| rs316009 | 6:160254732 | intron | C>T/G | – | 0.595 | |
| rs316019 | 6:160249250 | missense | C>A | Ala270Ser | 0.808 | |
| rs391300 | 17:2312964 | intron | C>T | – | 0.739 | |
| rs461473 | 6:160122530 | intron | G>A | – | 0.898 | |
| rs4810083 | 20:57545215 | intergenic | C>T | – | 0.145 | |
| rs578427 | – | 6:91702432 | intergenic | T>C | – | 0.909 |
| rs622342 | 6:160151834 | intron | A>C | – | 0.218 | |
| rs6265 | 11:27658369 | missense | C>T | Val66Met | monomorphic | |
| rs819 2675 | 3:171007094 | intron | C>T | – | 0.674 |
Genotype and allele frequencies of 13 single nucleotide polymorphism(s) demonstrating no significant association to type 2 diabetes mellitus treatment response.
| SNP | Genotype/ Allele | Control |
Uncontrolled |
OR (95% CI) | |
|---|---|---|---|---|---|
| rs10783050 | TT | 52 (98.1) | 86 (98.9) | reference | |
| TC | 1 (1.9) | 0 (0.0) | 0.20 (0.01-5.06) | 0.331 | |
| T | 105 (99.1) | 172 (98.9) | reference | ||
| C | 1 (0.9) | 0 (0.0) | 0.20 (0.01-5.05) | 0.332 | |
| rs1143623 | CC | 48 (90.6) | 74 (85.1) | reference | |
| CG | 5 (9.4) | 11 (12.6) | 1.43 (0.47-4.36) | 0.533 | |
| C | 96 (90.6) | 159 (91.4) | reference | ||
| G | 10 (9.4) | 11 (6.3) | 0.66 (0.27-1.62) | 0.369 | |
| rs13266634 | CC | 50 (94.3) | 78 (89.7) | reference | |
| CT | 3 (5.7) | 8 (9.2) | 1.71 (0.43-6.75) | 0.444 | |
| 100 (94.3) | 164 (94.3) | reference | |||
| 6 (5.7) | 8 (4.6) | 0.81 (0.27-2.41) | 0.709 | ||
| rs13376631 | AA | 16 (30.2) | 22 (25.3) | reference | |
| GG | 11 (20.8) | 17 (19.5) | 1.12 (0.42-3.04) | 0.818 | |
| AG | 25 (13.3) | 37 (42.5) | 1.08 (0.47-2.44) | 0.860 | |
| 57 (53.8) | 81 (46.6) | reference | |||
| 47 (44.3) | 71 (40.8) | 1.06 (0.64-1.75) | 0.811 | ||
| rs1801282 | CC | 53 (100.0) | 86 (98.9) | monomorphic | monomorphic |
| C | 106 (100.0) | 172 (98.9) | – | ||
| rs249429 | TT | 28 (52.8) | 40 (46.0) | reference | |
| CC | 3 (5.7) | 6 (6.9) | 1.40 (0.32-6.07) | 0.650 | |
| CT | 22 (41.5) | 40 (46.0) | 1.27 (0.6258-2.5885) | 0.510 | |
| T | 78 (73.6) | 120 (69.0) | reference | ||
| C | 28 (26.4) | 52 (29.9) | 1.21 (0.70-2.07) | 0.500 | |
| rs2815752 | GG | 18 34.0) | 22 (25.3) | reference | |
| AA | 13 (24.5) | 20 (23.0) | 1.26 (0.49-3.21) | 0.630 | |
| GA | 22 (41.5) | 43 (49.4) | 1.60 (0.71-3.59) | 0.254 | |
| 58 (54.7) | 87 (50.0) | reference | |||
| 48 (45.2) | 83 (47.7) | 1.15 (0.71-3.59) | 0.567 | ||
| rs34834489 | GG | 46 (86.7) | 80 (92.0) | reference | |
| GA | 6 (11.3) | 6 (6.9) | 0.58 (0.18-1.89) | 0.361 | |
| 98 (92.5) | 166 (95.4) | reference | |||
| 6 (5.7) | 6 (3.4) | 0.59 (0.19-1.88) | 0.373 | ||
| rs391300 | CC | 9 (17.0) | 17 (19.5) | reference | |
| TT | 18 (34.0) | 24 (27.6) | 0.71 (0.26-1.94) | 0.500 | |
| CT | 26 (49.1) | 44 (50.6) | 0.90 (0.35-02.30) | 0.819 | |
| 44 (41.5) | 78 (44.8) | reference | |||
| 62 (58.5) | 92 (52.9) | 0.84 (0.51-1.37) | 0.477 | ||
| rs461473 | GG | 52 (98.1) | 84 (96.6) | reference | |
| GA | 1 (1.9) | 2 (2.3) | 1.24 (0.11-14.00) | 0.863 | |
| 105 (99.1) | 170 (97.7) | reference | |||
| 1 (0.9) | 2 (1.1) | 1.24 (0.11-13.99) | 0.864 | ||
| rs622342 | AA | 33 (62.3) | 48 (55.2) | reference | |
| CC | 3 (5.7) | 12 (13.8) | 4.13 (0.87-19.65) | 0.075 | |
| CA | 18 (34.0) | 26 (29.9) | 0.99 (0.472.10) | 0.985 | |
| 84 (79.2) | 122 (70.1) | reference | |||
| 22 (20.8) | 50 (28.7) | 1.56 (0.88-2.78) | 0.113 | ||
| rs6265 | CC | 53 (100.0) | 86 (98.9) | monomorphic | monomorphic |
| C | 106 (100.0) | 172 (98.9) | – | – | |
| rs8192675 | CC | 42 (79.2) | 58 (66.7) | reference | |
| TT | 1 (1.9) | 3 (3.4) | 2.17 (0.22-21.62) | 0.508 | |
| CT | 9 (17.0) | 25 (28.7) | 2.01 (0.85-4.75) | 0.111 | |
| 93 (87.7) | 141 (81.0) | reference | |||
| 11 (10.4) | 31 (17.8 | 1.86 (0.89-3.88) | 0.099 |
Genotype and allele frequencies of four single nucleotide polymorphism(s) demonstrating no significant association to type 2 diabetes mellitus treatment response.
| Unadjusted | Adjusted | |||||||
|---|---|---|---|---|---|---|---|---|
| SNP | Genotype/ Allele | Controlled |
Uncontrolled |
OR (95% CI) | OR (95% CI) | Bonferonni Corrected |
||
| rs316009 | CC | 45 (84.9) | 83 (95.4) | reference | reference | |||
| CT | 8 (15.1) | 3 (0.03) | 0.20 (0.05-0.81) | 0.31 (0.05-0.190) | 0.204 | – | ||
| 98 (92.5) | 169 (97.1) | reference | reference | |||||
| 8 (0.08) | 3 (0.02) | 0.22 (0.06-0.84) | 0.85 (0.01-0.93) | 0.088 | ||||
| rs316019 | CC | 41 (77.4) | 77 (88.5) | reference | reference | |||
| AA | 1 (0.02) | 0 (0.0) | 0.18 (0.01-4.48) | 0.295 | ||||
| CA | 11 (20.8) | 8 (0.09) | 0.39 (0.14-1.04) | 0.059 | ||||
| C | 93 (87.7) | 162 (93.1) | reference | reference | ||||
| A | 13 (12.3) | 8 (0.05) | 0.35 (0.14-0.8) | 0.72 (0.21-2.44) | 0.593 | – | ||
| rs4810083 | CC | 16 (30.2) | 33 (37.9) | reference | reference | |||
| TT | 10 (18.9) | 32 (36.9) | 1.55 (0.61-3.92) | 0.353 | 1.24 (0.42-3.60) | 0.698 | – | |
| CT | 27 (35.7) | 21 (43.1) | 0.38 (0.17-0.86) | 2.80 (1.01-7.79) | 0.098 | |||
| 59 (55.7) | 75 (43.1) | reference | reference | |||||
| 47 (44.3) | 97 (55.7) | 1.62 (1.00-2.64) | 0.051 | 0.81 (0.48-1.36) | 0.423 | – | ||
| rs578427 | TT | 10 (18.9) | 15 (17.2) | reference | reference | |||
| CC | 4 (7.5) | 28 (32.2) | 4.67 (1.25-17.44) | 1.80 (0.58-5.64) | 0.312 | |||
| CT | 39 (73.6) | 43 (49.4) | 0.74 (0.30-1.83) | 0.507 | 1.70 (0.45-2.55) | 0.884 | ||
| T | 47 (44.3) | 73 (42.0) | reference | reference | ||||
| C | 59 (55.7) | 99 (56.9) | 1.08 (0.66-1.76) | 0.765 | 1.31 (0.78-2.22) | 0.308 | – | |
Clinical and biochemical demographics of the study population.
| Parameters | Controlled ( |
Uncontrolled ( |
|
|---|---|---|---|
| Sex (F; M) | F: 36; M: 14 | F: 57; M: 30 | – |
| Age (years) | 60.7 ± 11.0 | 58.3 ± 11.4 | 0.470 |
| Weight (kg) | 85.8 ± 19.5 | 85.4 ± 19.1 | 0.833 |
| Height (cm) | 162.1 ± 7.8 | 163.1 ± 7.7 | 0.487 |
| Body mass index | 31.9 ± 8.4 | 30.4 ± 10.7 | 0.304 |
| Hb A1c (%): | |||
| baseline | 7.6 ± 2.0 | 11.0 ± 2.9 | |
| 12 months | 6.7 ± 1.2 | 11.5 ± 2.9 | |
| Random blood sugar (%) | 9.4 ± 3.9 | 14.5 ± 6.6 | |
| Systolic blood pressure (mmHg) | 147.0 ± 24.0 | 153.5 ± 23.9 | 0.130 |
| Diastolic blood pressure (mmHg) | 83.9 ± 15.5 | 90.3 ± 13.7 | |
| Total cholesterol (mmol/L) | 4.4 ± 1.1 | 5.0 ± 1.1 | |
| High-density lipoprotein (mmol/L) | 1.2 ± 0.4 | 1.2 ± 0.4 | 0.672 |
| Low-density lipoprotein (mmol/L) | 2.3 ± 0.9 | 2.8 ± 0.9 | |
| Triglycerides (mmol/L) | 2.0 ± 1.2 | 2.3 ± 1.1 | 0.215 |
| Creatinine (g/mol) | 157.7 ± 383.1 | 79.3 ± 29.5 | 0.317 |
| Glomerular filtration rate (mL/min/1.73 m2 | 41.7 ± 21.5 | 52.6 ± 25.0 | 0.313 |