From: An update on vitamin B12-related gene polymorphisms and B12 status
Chromosome location | Gene name (gene symbol) | Reference SNP cluster ID | Sample size and ethnicity | Study design | Age (years) | Minor allele frequency | Effect size | P value | References |
---|---|---|---|---|---|---|---|---|---|
1p34.1 | Methylmalonic aciduria and homocystinuria type C protein (MMACHC) | rs10789465 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.469†| Not available | 1.00 × 10−3 | Andrew et al. [13] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801131 | n = 988 French women | Cross-sectional | 40–65 (range) | C = 0.290 | Not available | > 0.05 | De Batlle et al. [79] |
1p36.3 | Methylenetetrahydrofolate reductase (MTHFR) | Rs1801131 | n = 6784 Danish | Cross-sectional | 30–60 (range) | C = 0.340 | Not available | > 0.05 | Thuesen et al. [57] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | Rs1801131 | n = 220 Brazilian | Cross-sectional | 1–8 (range) | C = 0.240 | Not available | > 0.05 | Aléssio et al. [78] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 988 French women | Cross-sectional | 40–65 (range) | T = 0.360 | Not available | > 0.05 | De Batlle et al. [79] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 731 English (White Caucasian) | Cross-sectional | 85 | T = 0.330 | β = 5.00 × 10−5 pmol/l‡ | > 0.05 | Mendonca et al. [28] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | Elderly individuals: n = 262 Brazilian | Cross-sectional | 60–91 (range) | T = 0.370 | Not available | > 0.05 | Barnabe et al. [77] |
Children: n = 106 Brazilian | 0.5–6 (range) | T = 0.290 | Not available | > 0.05 | |||||
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 6784 Danish | Cross-sectional | 30–60 (range) | T = 0.290 | Effect allele: Not available Other allele: not available Low serum vitamin B12: OR 1·78 (95% CI 1.25, 2.54) pmol/l | 3.00 × 10−3 | Thuesen et al. [57] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 153 Spanish | Cross-sectional | 13–19 (range) | T = 0.380 | Not available | > 0.05 | Al-Tahan et al. [81] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 10,601 Norwegian | Cross-sectional | 56 | T = 0.280 | Not available | > 0.05 | Hustad et al. [80] |
1p36.3 | Methylenetetrahydrofolate Reductase (MTHFR) | rs1801133 | n = 220 Brazilian | Cross-sectional | 1–8 (range) | T = 0.320 | Not available | > 0.05 | Aléssio et al. [78] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs1805087 | n = 731 English (White Caucasian) | Cross-sectional | 85 | G = 0.180 | β = 4.00 × 10−3 pmol/l‡ | > 0.05 | Mendonca et al. [28] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs1805087 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.161†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs1805087 | n = 6784 Danish | Cross-sectional | 30–60 (range) | G = 0.200 | Not available | > 0.05 | Thuesen et al. [57] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs2275568 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.460†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs2789352 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.381†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs3768142 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.384†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTR) | rs10733118 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.381†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-Homocysteine methyltransferase (MTR) | rs10925257 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.155†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTR) | rs11800413 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.431†| Not available | > 0.05 | Andrew et al. [13] |
1q43 | 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTR) | rs12060264 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.438†| Not available | > 0.05 | Andrew et al. [13] |
2q23.2 | Methylmalonic aciduria and homocystinuria,CblD type (MMADHC) | rs7580915 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.228†| Not available | > 0.05 | Andrew et al. [13] |
4p14 | Replication factor C subunit 1 (RFC1) | rs1051266 | Elderly individuals: n = 262 Brazilian | Cross-sectional | 60–91 (range) | A = 0.430 | Not available | > 0.05 | Barnabe et al. [77] |
Children: n = 106 Brazilian | 1–6 (range) | A/G = 0.500 | Not available | > 0.05 | |||||
4q31.21 | Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) | rs4835011 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.080†| Not available | > 0.05 | Andrew et al. [13] |
4q31.21 | Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) | rs4835012 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.178†| Not available | 3.00 × 10−2 | Andrew et al. [13] |
4q31.21 | Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) | rs4835014 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.031†| Not available | > 0.05 | Andrew et al. [13] |
4q31.21 | Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) | rs11728906 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.235†| Not available | > 0.05 | Andrew et al. [13] |
5q14.1 | Betaine-homocysteine S-methyltransferase (BHMT) | rs3733890 | n = 6784 Danish | Cross-sectional | 30–60 (range) | A = 0.290 | Not available | > 0.05 | Thuesen et al. [57] |
5p15.31 | Methionine synthase reductase (MTRR) | rs10380 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.156†| Not available | > 0.05 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs162031 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.205†| Not available | > 0.05 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs162036 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.186†| Not available | 4.00 × 10−2 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs162040 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.124†| Not available | > 0.05 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs162048 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.164†| Not available | 5.00 × 10−2 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs326120 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.155†| Not available | > 0.05 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs1532268 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.308†| Not available | 1.00 × 10−2 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs1801394 | n = 6784 Danish | Cross-sectional | 30–60 (range) | A = 0.430 | Not available | > 0.05 | Thuesen et al. [57] |
5p15.31 | Methionine synthase reductase (MTRR) | rs1801394 | n = 220 Brazilian | Cross-sectional | 1–8 (range) | A = 0.490 | Not available | > 0.05 | Aléssio et al. [78] |
5p15.31 | Methionine synthase reductase (MTRR) | rs2966952 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.167†| Not available | > 0.05 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs3776455 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.389†| Not available | 2.00 × 10−3 | Andrew et al. [13] |
5p15.31 | Methionine synthase reductase (MTRR) | rs6555501 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.473†| Not available | > 0.05 | Andrew et al. [13] |
6p12.3 | Methylmalonyl-CoA mutase (MUT) | rs6458687 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.372†| Not available | > 0.05 | Andrew et al. [13] |
6p12.3 | Methylmalonyl-CoA mutase (MUT) | rs6458690 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.363†| Not available | 2.00 × 10− 4 | Andrew et al. [13] |
6p12.3 | Methylmalonyl-CoA mutase (MUT) | rs9381784 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.363†| Not available | 3.00 × 10−2 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs991974 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.044†| Not available | > 0.05 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs1457498 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.084†| Not available | > 0.05 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs3778241 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.398†| Not available | > 0.05 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs3799105 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.384†| Not available | > 0.05 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs6455338 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.387†| Not available | > 0.05 | Andrew et al. [13] |
6q13 | LMBR1 domain containing 1 (LMBRD1) | rs9294851 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | T = 0.384†| Not available | > 0.05 | Andrew et al. [13] |
11q12.1 | Transcobalamin 1 (TCN1) | rs526934 | n = 731 English (White Caucasian) | Cross-sectional | 85 | G = 0.270 | β = 4.00 × 10−3 pmol/l‡ | > 0.05 | Mendonca et al. [28] |
12q24.11 | Methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) | rs2287182 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.128†| Not available | > 0.05 | Andrew et al. [13] |
12q24.11 | Methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) | rs3759387 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.235†| Not available | > 0.05 | Andrew et al. [13] |
12q24.11 | Methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) | rs7134594 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | C = 0.487†| Not available | > 0.05 | Andrew et al. [13] |
12q24.11 | Methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) | rs7957619 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | A = 0.110 †| Not available | > 0.05 | Andrew et al. [13] |
12q24.11 | Methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) | rs12314392 | n = 262 Caucasian women of North European descent | Cross-sectional (Twin Study) | 48 ± 13 | G = 0.433 †| Not available | > 0.05 | Andrew et al. [13] |
19p13.2 | CD320 molecule (CD320)/transcobalamin II receptor (TcblR) | rs2336573 | n = 591 Caucasian women | Cross-sectional | 77 ± 7 | A = 0.050 | Not available | > 0.05 | Kurnat-Thoma et al. [59] |
n = 198 African American women | 75 ± 6 | A = 0.330 | Not available | 4.0 × 10−2 | |||||
n = 797 Combined total |  |  | Not available | 2.0 × 10−2 | |||||
19q13.33 | Fucosyl transferase 2 gene (FUT2) | rs492602 | n = 731 English (White Caucasian) | Cross-sectional | 85 | A = 0.450 | β = 0.05 pmol/l‡ | < 0.001 | Mendonca et al. [28] |
19q13.33 | Fucosyl transferase 2 gene (FUT2) | rs602662 | Vegetarian: n = 553 North Indian | Cross-sectional | 50 (41–59) Median (interquartile range) | A = 0.310 | Effect: A allele Other: G allele β = 0.12 pmol/l | 5.0 × 10−3 | Tanwar et al. [27] |
Non-vegetarian: n = 593 North Indian | Cross-sectional | 47 (37–55) Median (interquartile range) | Effect: A allele Other: G allele β = 0.12 pmol/l | 4.0 × 10−3 | |||||
Combined total: n = 1146 North Indian | Cross-sectional | 49 (40–57) Median (interquartile range) | Effect: A allele Other: G allele β = 0.12 pmol/l | 4.0 × 10−5 | |||||
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | NORCAP cohort*: n = 2411 Norwegian Serum holoTC could be analysed in only 2379 individuals | Cross-sectional | 50–64 (range) | G = 0.440 | Effect: C allele Other: G allele Total holo-TC: β = 0.02 pmol/l‡ | > 0.05‡ | Riedel et al. [55] |
Effect: C allele Other: G allele Plasma Cbl: β = 0.03 pmol/l‡ | > 0.05‡ | ||||||||
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | n = 122 Portuguese | Cross-sectional | 46 ± 13 | G = 0.480 | Not available | Vitamin B12: > 0.05 Holo-TC: < 0.05 | Castro et al. [52] |
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | n = 554 Participants of Latino ancestry residing in USA | Cross-sectional | 69 ± 6 | G = 0.350 | Not available | Vitamin B12: > 0.05 Total holo TC: > 0.05 | Garrod et al. [56] |
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | n = 613 Northern Irish Men (Caucasian) | Cross-sectional | 30–49 (range) | G = 0.450 | Not available | 1.00 × 10−2 | Stanislawska-Sachadyn et al. [54] |
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | n = 6784 Danish | Cross-sectional | 30–60 (range) | G = 0.440 | Not available | > 0.05 | Thuesen et al. [57] |
22q12.2 | Transcobalamin 2 (TCN2) | rs1801198 | n = 207 Brazillian | Cross-sectional | 1–8 (range) | G = 0.360 | Not available | > 0.05 | Alessio et al. [58] |
22q12.2 | Transcobalamin 2 (TCN2) | rs4820888 | n = 591 Caucasian women | Cross-sectional | 77 ± 7 | G = 0.430 | Not available | > 0.05 | Kurnat-Thoma et al. [59] |
n = 198 African American women | 75 ± 6 | G = 0.450 | Not available | > 0.05 | |||||
n = 797 Combined total |  |  | Not available | 2.0 × 10−2 | |||||
22q12.2 | Transcobalamin 2 (TCN2) | rs9606756 | NORCAP cohort*: n = 2411 Norwegian Serum holoTC could be analysed in only 2379 individuals | Cross-sectional | 50–64 (range) | G = 0.120 | Effect: A allele Other: G allele Total holo-TC: β = − 0.21 pmol/l‡ | < 0.001‡ | Riedel et al. [55] |
Effect: A allele Other: G allele Plasma Cbl: β = −0.02 pmol/l‡ | > 0.05‡ | ||||||||
22q12.2 | Transcobalamin 2 (TCN2) | rs9606756 | n = 6784 Danish | Cross-sectional | 30–60 (range) | G = 0.120 | Not available | > 0.05 | Thuesen et al. [57] |
1p36.3 19q13.33 | Methylenetetrahydrofolate Reductase (MTHFR) + Fucosyl transferase 2 gene (FUT2) | rs180133 rs180131 rs492602 | n = 988 Brazillian | Cross-sectional | 5 ± 3 | rs180133 T = 0.320 rs180131 C = 0.220 rs492602 G = 0.390 | β for GRS = − 0·11 pmol/l | < 0·001 | Cobayashi et al. [105] |