Table 2.
Comparison of distribution of MTX-related enzyme gene and transporter polymorphisms among ethnic or population group in the patients with rheumatoid arthritis
| Ethnic/Population group | n | Genotype frequency (n) | HWE | Allele frequency (%) | p-value | Reference No. | |||
|---|---|---|---|---|---|---|---|---|---|
| MTHFR 1298 | A/A | A/C | C/C | A | C | ||||
| Japanese (Our study) | 159 | 109 (68.6) | 42 (26.4) | 8 (5.0) | 0.149 | 82 | 18 | ||
| Japanese | 357 | 232 (65.0) | 107 (30.0) | 18 (5.0) | 0.224 | 80 | 20 | 0.7070 | [5, 6, 20, 21] |
| Chinese | 93 | 63 (67.7) | 29 (31.2) | 1 (1.1) | 0.237 | 83 | 27 | 0.1690 | [22] |
| Caucasian | 1828 | 809 (44.3) | 785 (42.9) | 234 (12.8) | 0.045 | 66 | 34 | p<0.0001 | [23–31] |
| African-American | 138 | 102 (74.0) | 35 (25.0) | 1 (1.0) | 0.278 | 87 | 13 | 0.0614 | [26] |
| TYMS 3'-UTR | −6/−6 | −6/+6 | +6/+6 | −6 | +6 | ||||
| Japanese (Our study) | 159 | 72 (45.3) | 67 (42.1) | 20 (12.6) | 0.477 | 66 | 34 | ||
| Japanese | 409 | 173 (42.3) | 193 (47.2) | 43 (10.5) | 0.314 | 66 | 34 | 0.5180 | [6, 9, 32] |
| Caucasian | 98 | 10 (10.2) | 37 (37.8) | 51 (52.0) | 0.053 | 29 | 71 | < 0.0001 | [24] |
| RFC1 80 | G/G | G/A | A/A | G | A | ||||
| Japanese (Our study) | 159 | 34 (21.4) | 74 (46.5) | 51 (32.1) | 0.461 | 45 | 55 | ||
| Japanese | 681 | 135 (19.8) | 348 (51.1) | 198 (29.1) | 0.421 | 45 | 55 | 0.5820 | [5, 9, 20, 21, 32, 33] |
| Caucasian | 611 | 187 (30.6) | 275 (45.0) | 149 (24.4) | 0.017 | 53 | 47 | 0.0360 | [24, 34–36] |
| RFC1−43 | T/T | T/C | C/C | T | C | ||||
| Japanese (Our study) | 159 | 34 (21.4) | 74 (46.5) | 51 (32.1) | 0.461 | 45 | 55 | ||
| Caucasian | 106 | 39 (36.8) | 47 (44.3) | 20 (18.9) | 0.388 | 59 | 41 | 0.0760 | [34] |
| FPGS 1994 | G/G | G/A | A/A | G | A | ||||
| Japanese (Our study) | 159 | 70 (44.0) | 73 (45.9) | 16 (10.1) | 0.632 | 67 | 33 | ||
| Caucasian | 205 | 42 (21.0) | 99 (48.0) | 64 (31.0) | 0.743 | 45 | 55 | < 0.0001 | [37] |
| GGH 452 | C/C | C/T | T/T | C | T | ||||
| Japanese (Our study) | 159 | 134 (84.3) | 22 (13.8) | 3 (1.9) | 0.081 | 91 | 9 | ||
| Japanese | 142 | 129 (90.8) | 13 (9.2) | 0 (0.0) | 0.568 | 95 | 5 | 0.1070 | [20, 21] |
| Caucasian | 571 | 479 (83.9) | 91 (15.9) | 1 (0.2) | 0.119 | 92 | 8 | 0.0300 | [27, 37, 38] |
| GGH−401 | C/C | C/T | T/T | C | T | ||||
| Japanese (Our study) | 159 | 88 (55.3) | 62 (39.0) | 9 (5.7) | 0.654 | 75 | 25 | ||
| Japanese | 257 | 169 (65.8) | 78 (30.3) | 10 (3.9) | 0.790 | 81 | 19 | 0.1010 | [21, 32] |
| ABCB1 3435 | C/C | C/T | T/T | C | T | ||||
| Japanese (Our study) | 159 | 54 (34.0) | 82 (51.6) | 23 (14.4) | 0.363 | 60 | 40 | ||
| Japanese | 174 | 61 (35.0) | 80 (46.0) | 33 (19.0) | 0.460 | 58 | 42 | 0.4570 | [9, 20] |
| Caucasian | 769 | 178 (23.1) | 381 (49.5) | 210 (27.3) | 0.838 | 48 | 52 | 0.0010 | [27, 28, 36, 39] |
| ABCC2 IVS23 + 56 | T/T | T/C | C/C | T | C | ||||
| Japanese (Our study) | 159 | 6 (3.8) | 55 (34.6) | 98 (61.6) | 0.614 | 21 | 79 | ||
| Caucasian | 309 | 122 (39.5) | 149 (48.2) | 38 (12.3) | 0.467 | 64 | 36 | < 0.0001 | [27, 40] |
| ABCG2 914 | C/C | C/A | A/A | C | A | ||||
| Japanese (Our study) | 159 | 77 (48.4) | 67 (42.1) | 15 (9.5) | 0.939 | 69 | 31 | ||
| Japanese | 55 | 30 (54.5) | 20 (36.4) | 5 (9.1) | 0.537 | 73 | 27 | 0.7230 | [14] |
| Caucasian | 190 | 149 (78.4) | 40 (21.1) | 1 (0.5) | 0.330 | 89 | 11 | < 0.0001 | [27] |
Values are given as n (%). HWE: p-value for chi-square test for agreement with Hardy-Weinberg equilibrium. p-value; comparison our study (Japanese) with each ethnic/population group
MTHFR: methylenetetrahydrofolate reductase, TYMS: thymidylate synthase, RFC1: reduced folate carrier 1, FPGS: folypolyglutamayl synthase, GGH: γ-glutamyl hydrolase, ABCB1: ATP binding cassette subfamily B member 1, ABCC2: ATP binding cassette subfamily C member 2, ABCG2: ATP binding cassette subfamily G member 2