Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms
Abstract
:1. Introduction
2. Arsenic Methylation by Human AS3MT
3. Association of Arsenic Methylation with Genotypes in Human AS3MT
3.1. In Vitro Studies
3.2. Human Case Studies
3.2.1. Mexico
3.2.2. Argentina
3.2.3. Chile
3.2.4. Central Europe
3.2.5. India
3.2.6. Taiwan
3.2.7. Vietnam
4. Allele Frequency of SNPs in AS3MT
5. Conclusions and Future Perspectives
Acknowledgments
References
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SNP ID | rs # | Location | Nucleotide change | Ancestral | Allele | Japanese (n = 141) | South Koreans (n = 230) | Chinese (n = 54) | Mongolians (n = 58) | Tibetans (n = 65) | Nepalese (n = 31) |
---|---|---|---|---|---|---|---|---|---|---|---|
3963 | rs7098825 | 5′ terminal | C/T | T | C | 0.266 | 0.298 | 0.241 | 0.009 | 0.331 | 0.355 |
T | 0.734 | 0.702 | 0.759 | 0.991 | 0.669 | 0.645 | |||||
4602 | rs7085104 | 5′ terminal | A/G | A | A | 0.567 | 0.565 | 0.436 | 0.672* | 0.454 | 0.694 |
G | 0.433 | 0.435 | 0.565 | 0.327* | 0.546 | 0.307 | |||||
4740 | rs12416687 | 5′ terminal | C/T | T | C | 0.060 | 0.067 | 0.130 | 0.061 | 0.054 | 0.000 |
T | 0.940 | 0.933 | 0.871 | 0.940 | 0.946 | 1.000 | |||||
5913 | rs4917986 | Intron 3 | C/T | T | C | NA | NA | NA | NA | NA | NA |
T | NA | NA | NA | NA | NA | NA | |||||
6144 | rs17878846 | Intron 3 | A/T | A | A | 0.734 | 0.730 | 0.695* | 0.931 | 0.708* | 0.678 |
T | 0.266 | 0.270 | 0.306* | 0.069 | 0.292* | 0.323 | |||||
7395 | rs12767543 | Intron 3 | A/G | G | A | 0.287 | 0.274* | 0.426 | 0.069 | 0.185 | 0.275 |
G | 0.713 | 0.727* | 0.574 | 0.931 | 0.815 | 0.726 | |||||
8979 | rs7920657 | Intron 5 | A/T | T | A | 0.057 | 0.076 | 0 | 0.077 | 0.069 | 0.000 |
T | 0.944 | 0.924 | 1.000 | 0.922 | 0.931 | 1.000 | |||||
9749 | rs17881367 | Intron 5 | A/G | A | A | 0.944 | 0.924 | 1.000 | 0.922* | 0.931 | 1.000 |
G | 0.057 | 0.076 | 0 | 0.077* | 0.069 | 0.000 | |||||
10209 | rs3740394 | Intron 6 | A/G | T | A | 0.990 | 0.985 | 1.000 | 0.983 | 0.985 | 0.984 |
G | 0.011 | 0.015 | 0 | 0.017 | 0.016 | 0.016 | |||||
12390 | rs3740393 | Intron 6 | C/G | C | C | 0.373* | 0.279 | 0.278 | 0.431 | 0.338 | 0.339 |
G | 0.628* | 0.722 | 0.722 | 0.569 | 0.662 | 0.661 | |||||
12590 | rs3740392 | Intron 7 | C/T | T | C | 0.178* | 0.172 | 0.251 | 0.215 | 0.185 | 0.162 |
T | 0.823* | 0.829 | 0.751 | 0.784 | 0.816 | 0.839 | |||||
14215 | rs3740390 | Intron 8 | C/T | C | C | 0.483* | 0.587* | 0.343 | 0.587* | 0.262 | 0.645 |
T | 0.518* | 0.413* | 0.658 | 0.414* | 0.739 | 0.355 | |||||
144581 | rs11191439 | Exon 9 | C/T | T | C | 0.004 | 0.009 | 0 | 0.026 | 0.023 | 0.000 |
T | 0.997 | 0.992 | 1.000 | 0.974 | 0.977 | 1.000 | |||||
25986 | rs7085854 | Intron 8 | C/T | T | C | 0.057 | 0.122 | 0.259 | 0.052 | 0.162 | 0.145 |
T | 0.944 | 0.879 | 0.741 | 0.949 | 0.839 | 0.855 | |||||
26790 | rs11191445 | Intron 10 | C/T | C | C | 0.990* | 0.985 | 1.000 | 0.983 | 0.977 | 0.968 |
T | 0.011* | 0.015 | 0 | 0.017 | 0.023 | 0.033 | |||||
27215 | rs11191446 | Intron 10 | A/G | A | A | 0.926 | 0.918 | 0.972 | 0.949 | 0.900 | 0.952 |
G | 0.075 | 0.083 | 0.028 | 0.052 | 0.100 | 0.049 | |||||
35587 | rs11191453 | Intron 10 | C/T | T | C | 0.344* | 0.370* | 0.333 | 0.155* | 0.516* | 0.404 |
T | 0.656* | 0.631* | 0.666 | 0.845* | 0.485* | 0.597 | |||||
35991 | rs10748835 | Intron 10 | A/G | A | A | 0.543 | 0.570 | 0.602 | 0.561 | 0.654 | 0.597 |
G | 0.457 | 0.431 | 0.398 | 0.440 | 0.346 | 0.404 | |||||
37616 | rs4568943 | 3′ terminal | A/C | A | A | 0.656* | 0.735 | 0.519* | 0.906* | 0.639 | 0.678 |
C | 0.344* | 0.266 | 0.482* | 0.095* | 0.362 | 0.323 | |||||
37853 | rs11191459 | 3′ terminal | A/G | G | A | NA | NA | NA | NA | NA | NA |
G | NA | NA | NA | NA | NA | NA | |||||
37950 | rs17879819 | 3′ terminal | C/T | C | C | 0.710 | 0.713 | 0.676 | 0.923 | 0.638 | 0.629 |
T | 0.291 | 0.287 | 0.324 | 0.078 | 0.361 | 0.371 | |||||
References | [65] | [65] | [65] | [65] | [65] | [65] |
SNP ID | rs # | Location | Nucleotide change | Ancestral | Allele | Vietnamese (n = 100) | Sri Lanka-Tamils (n = 29) | Sri Lanka-Sinhalese (n = 30) | Ovambos (n = 102) | Ghanaians (n = 87) |
---|---|---|---|---|---|---|---|---|---|---|
3963 | rs7098825 | 5′ terminal | C/T | T | C | NA | 0.086 | 0.117 | 0.054 | 0.121 |
T | NA | 0.914 | 0.883 | 0.946 | 0.879 | |||||
4602 | rs7085104 | 5′ terminal | A/G | A | A | 0.420 | 0.845 | 0.817 | 0.525 | 0.598 |
G | 0.580 | 0.155 | 0.184 | 0.475 | 0.403 | |||||
4740 | rs12416687 | 5′ terminal | C/T | T | C | 0 | 0.017 | 0.017 | 0.133 | 0.104 |
T | 0.720 | 0.983 | 0.984 | 0.868 | 0.897 | |||||
5913 | rs4917986 | Intron 3 | C/T | T | C | 0.080 | NA | NA | NA | NA |
T | 0.920 | NA | NA | NA | NA | |||||
6144 | rs17878846 | Intron 3 | A/T | A | A | 0.750 | 0.845 | 0.867 | 1.000 | 1.000 |
T | 0.250 | 0.155 | 0.134 | 0 | 0 | |||||
7395 | rs12767543 | Intron 3 | A/G | G | A | 0.335* | 0.121 | 0.167 | 0.113 | 0.304 |
G | 0.665* | 0.880 | 0.834 | 0.888 | 0.695 | |||||
8979 | rs7920657 | Intron 5 | A/T | T | A | 0 | 0.035 | 0.017 | 0.142 | 0.075 |
T | 0.590 | 0.966 | 0.984 | 0.858 | 0.926 | |||||
9749 | rs17881367 | Intron 5 | A/G | A | A | NA | 0.966 | 0.984 | 0.858 | 0.926 |
G | NA | 0.035 | 0.017 | 0.142 | 0.075 | |||||
10209 | rs3740394 | Intron 6 | A/G | T | A | NA | 0.983 | 0.984 | 0.868 | 0.920 |
G | NA | 0.017 | 0.017 | 0.133 | 0.081 | |||||
12390 | rs3740393 | Intron 6 | C/G | C | C | 0.225 | 0.189 | 0.251 | 0.540 | 0.299 |
G | 0.775 | 0.810 | 0.751 | 0.461 | 0.702 | |||||
12590 | rs3740392 | Intron 7 | C/T | T | C | 0.360 | 0.155 | 0.084 | 0.221 | 0.189 |
T | 0.640 | 0.845 | 0.917 | 0.780 | 0.810 | |||||
14215 | rs3740390 | Intron 8 | C/T | C | C | 0.755 | 0.810 | 0.867 | 0.554 | 0.414* |
T | 0.245 | 0.189 | 0.134 | 0.446 | 0.587* | |||||
144581 | rs11191439 | Exon 9 | C/T | T | C | 0 | 0 | 0.017 | 0.093 | 0.075 |
T | 0.980 | 1.000 | 0.984 | 0.907 | 0.926 | |||||
25986 | rs7085854 | Intron 8 | C/T | T | C | NA | 0.172 | 0.250 | 0.299 | 0.316 |
T | NA | 0.828 | 0.750 | 0.701 | 0.684 | |||||
26790 | rs11191445 | Intron 10 | C/T | C | C | NA | 0.983 | 0.984 | 0.814 | 0.966 |
T | NA | 0.017 | 0.017 | 0.186 | 0.035 | |||||
27215 | rs11191446 | Intron 10 | A/G | A | A | NA | 0.966 | 0.984 | 0.873 | 0.920 |
G | NA | 0.035 | 0.017 | 0.128 | 0.081 | |||||
35587 | rs11191453 | Intron 10 | C/T | T | C | 0.270* | 0.207 | 0.134 | 0.045 | 0.063 |
T | 0.730* | 0.793 | 0.867 | 0.957 | 0.937 | |||||
35991 | rs10748835 | Intron 10 | A/G | A | A | 0.585 | 0.535 | 0.367 | 0.706 | 0.402 |
G | 0.415 | 0.466 | 0.633 | 0.294 | 0.598 | |||||
37616 | rs4568943 | 3′ terminal | A/C | A | A | NA | 0.794 | 0.867 | 0.941* | 0.931 |
C | NA | 0.207 | 0.134 | 0.059* | 0.069 | |||||
37853 | rs11191459 | 3′ terminal | A/G | G | A | 0.495 | NA | NA | NA | NA |
G | 0.505 | NA | NA | NA | NA | |||||
37950 | rs17879819 | 3′ terminal | C/T | C | C | NA | 0.793 | 0.867 | 0.961* | 0.937 |
T | NA | 0.207 | 0.134 | 0.040* | 0.063 | |||||
References | [20] | [65] | [65] | [65] | [65] |
SNP ID | rs # | Location | Nucleotide change | Ancestral | Mexico (n = 144) | Mexico (n = 122) | Mexico (n = 405) | Argentina (n = 147) |
---|---|---|---|---|---|---|---|---|
3963 | rs7098825 | 5′ terminal | C/T | T | ||||
4602 | rs7085104 | 5′ terminal | A/G | A | NS | %MMA[III + V]: AA + AG > GG %DMA[III + V]: GG > AA + AG DMA[III + V]/MMA[III + V]: GG > AA + AG | ||
4740 | rs12416687 | 5′ terminal | C/T | T | NS | |||
4965 | rs17881215 | Exon 1: 5′ UTR | C/G | G | ||||
5019 | rs17880342 | Exon 1: 5′ UTR | C/T | C | NA | |||
5051 | rs17883409 | Intron 1 | * | NAV | NS | NA | ||
5194 | rs3740400 | Intron 1 | A/C | C | NA | |||
5913 | rs4917986 | Intron 3 | C/T | T | ||||
6144 | rs17878846 | Intron 3 | A/T | A | ||||
7395 | rs12767543 | Intron 3 | A/G | G | DMA[V]/MMA[V]: AA + AG > GG2 | S | ||
8788 | rs17881367 | Intron 5 | -/TTT | NAV | NA | |||
8979 | rs7920657 | Intron 5 | A/T | T | ||||
9749 | rs17881367 | Intron 5 | A/G | A | ||||
10209 | rs3740394 | Intron 6 | C/T | T | NS | |||
12390 | rs3740393 | Intron 6 | C/G | C | DMA[V]/MMA[V]: CC + CG > GG2 | S | %MMA[V]: GG > CC, CG %DMA[V]: CC, CG > GG DMA[V]/MMA[V]: CC, CG > GG | |
12590 | rs3740392 | Intron 7 | C/T | T | NS | NA | ||
13599 | rs10883797 | Intron 7 | C/G | C | NS | |||
14215 | rs3740390 | Intron 8 | C/T | C | S | %MMA[V]: CC > TT, CT %DMA[V]: TT, CT > CC DMA[V]/MMA[V]: TT, CT > CC | ||
144581 | rs11191439 | Exon 9 | C/T | T | %MMA[III + V]: CT + CC > TT %As[V]: CT + CC > TT | NS | NA | |
25986 | rs7085854 | Intron 9 | C/T | T | NS | |||
27215 | rs11191446 | Intron 10 | A/G | A | ||||
30312 | rs1191453 | Intron 10 | C/T | T | DMA[V]/MMA[V]: CC > CT > TT | |||
35587 | rs11191453 | Intron 10 | C/T | T | DMA[V]/MMA[V]: CC + CT > TT2 MMA[V]/As[III]: TT > CC + CT2 | NS | S | |
35739 | rs11191454 | Intron 10 | A/G | A | S | |||
35991 | rs10748835 | Intron 10 | A/G | A | %MMA[V]: GG > AA, AG %DMA[V]: AA, AG > GG DMA[V]/MMA[V]: AA, AG > GG | |||
36209 | rs17879039 | Exon 11: 3′ UTR | A/G | G | ||||
37219 | rs1046778 | Exon 11: 3′ UTR | C/T | T | S | |||
37616 | rs4568943 | 3′ terminal | A/C | A | ||||
37853 | rs11191459 | 3′ terminal | A/G | G | ||||
37950 | rs17879819 | 3′ terminal | C/T | C | ||||
LD cluster | ||||||||
LD1 | 7395-12390-35587 | 7395-12390-14215-30312 -35587-35739-37219 | 12390-14215-35991 | |||||
LD2 | ||||||||
LD3 | ||||||||
LD4 | ||||||||
References | [35, 36] | [37] | [38] | [40] |
SNP ID | rs # | Location | Nucleotide change | Ancestral | Argentina (n = 104) | Chile (n = 50) | Chile (n = 207) |
---|---|---|---|---|---|---|---|
3963 | rs7098825 | 5′ terminal | C/T | T | |||
4602 | rs7085104 | 5′ terminal | A/G | A | %MMA[V]: AA + AG > GG %DMA[V]: GG > AG + AA | ||
4740 | rs12416687 | 5′ terminal | C/T | T | |||
4965 | rs17881215 | Exon 1: 5′ UTR | C/G | G | %MMA: CG > GG | ||
5019 | rs17880342 | Exon 1: 5′ UTR | C/T | C | |||
5051 | rs17883409 | Intron 1 | * | NAV | |||
5194 | rs3740400 | Intron 1 | A/C | C | %MMA[V]: AA + AC > CC %DMA[V]: CC > AC + AA | NS | |
5913 | rs4917986 | Intron 3 | C/T | T | |||
6144 | rs17878846 | Intron 3 | A/T | A | |||
7395 | rs12767543 | Intron 3 | A/G | G | |||
8788 | rs17881367 | Intron 5 | -/TTT | NAV | |||
8979 | rs7920657 | Intron 5 | A/T | T | |||
9749 | rs17881367 | Intron 5 | A/G | A | |||
10209 | rs3740394 | Intron 6 | C/T | T | |||
12390 | rs3740393 | Intron 6 | C/G | C | |||
12590 | rs3740392 | Intron 7 | C/T | T | |||
13599 | rs10883797 | Intron 7 | C/G | C | |||
14215 | rs3740390 | Intron 8 | C/T | C | |||
144581 | rs11191439 | Exon 9 | C/T | T | %MMA: CT + CC > TT | %MMA: CT + CC > TT | |
25986 | rs7085854 | Intron 9 | C/T | T | |||
27215 | rs11191446 | Intron 10 | A/G | A | |||
30312 | rs1191453 | Intron 10 | C/T | T | |||
35587 | rs11191453 | Intron 10 | C/T | T | |||
35739 | rs11191454 | Intron 10 | A/G | A | |||
35991 | rs10748835 | Intron 10 | A/G | A | |||
36209 | rs17879039 | Exon 11: 3′ UTR | A/G | G | NS | ||
37219 | rs1046778 | Exon 11: 3′ UTR | C/T | T | |||
37616 | rs4568943 | 3′ terminal | A/C | A | |||
37853 | rs11191459 | 3′ terminal | A/G | G | |||
37950 | rs17879819 | 3′ terminal | C/T | C | |||
LD cluster | |||||||
LD1 | 4602-5194-12390-14215-359913 | 4965-14458 | |||||
LD2 | |||||||
LD3 | |||||||
LD4 | |||||||
References | [43] | [44] | [45] |
SNP ID | rs # | Location | Nucleotide change | Ancestral | Central Europe4 (n = 415) | Taiwan (n = 208) | Vietnam (n = 100) |
---|---|---|---|---|---|---|---|
3963 | rs7098825 | 5′ terminal | C/T | T | NS | ||
4602 | rs7085104 | 5′ terminal | A/G | A | %DMA[V]: AA, AG > GG | ||
4740 | rs12416687 | 5′ terminal | C/T | T | %DMA[V]: TT > CT, CC | ||
4965 | rs17881215 | Exon 1: 5′ UTR | C/G | G | |||
5019 | rs17880342 | Exon 1: 5′ UTR | C/T | C | |||
5051 | rs17883409 | Intron 1 | * | NAV | |||
5194 | rs3740400 | Intron 1 | A/C | C | |||
5913 | rs4917986 | Intron 3 | C/T | T | %MMA[V]: CT > TT | ||
6144 | rs17878846 | Intron 3 | A/T | A | NS | ||
7395 | rs12767543 | Intron 3 | A/G | G | NS | ||
8788 | rs17881367 | Intron 5 | -/TTT | NAV | |||
8979 | rs7920657 | Intron 5 | A/T | T | %DMA[V]: AT, TT > AA | ||
9749 | rs17881367 | Intron 5 | A/G | A | %MMA[V]: AG > AA | ||
10209 | rs3740394 | Intron 6 | C/T | T | |||
12390 | rs3740393 | Intron 6 | C/G | C | %MMA[V]: GG > CG %DMA[V]: CG > GG DMA[V]/MMA[V]: CG > GG | %MMA[V]: GG > CC DMA[V]/MMA[V]: CG > GG | |
12590 | rs3740392 | Intron 7 | C/T | T | %DMA[V]: TT > CC DMA[V]/MMA[V]: TT > CC | ||
13599 | rs10883797 | Intron 7 | C/G | C | |||
14215 | rs3740390 | Intron 8 | C/T | C | NS | ||
144581 | rs11191439 | Exon 9 | C/T | T | %DMA[V]: TT > CT + CC %MMA[V]: CT + CC > TT | MMA[V]/IA: CT > TT | |
25986 | rs7085854 | Intron 9 | C/T | T | |||
27215 | rs11191446 | Intron 10 | A/G | A | %MMA[V]: AG > AA DMA[V]/MMA[V]: AA > AG MMA[V]/IA: AG > AA | ||
30312 | rs1191453 | Intron 10 | C/T | T | |||
35587 | rs11191453 | Intron 10 | C/T | T | DMA[V]/MMA[V]: CT > TT | ||
35739 | rs11191454 | Intron 10 | A/G | A | |||
35991 | rs10748835 | Intron 10 | A/G | A | %DMA[V]: AG > AA | ||
36209 | rs17879039 | Exon 11: 3′ UTR | A/G | G | |||
37219 | rs1046778 | Exon 11: 3′ UTR | C/T | T | |||
37616 | rs4568943 | 3′ terminal | A/C | A | |||
37853 | rs11191459 | 3′ terminal | A/G | G | %DMA[V]: GG, AG > AA %MMA[V]: GG > AA | ||
37950 | rs17879819 | 3′ terminal | C/T | C | NS | ||
LD cluster | |||||||
LD1 | 3963-6144-12390-14215-35587-37950 | ||||||
LD2 | 4602-35991-37853 | ||||||
LD3 | 4740-12590 | ||||||
LD4 | 5913-9749-27215 | ||||||
References | [46] | [49] | [18, 20] |
© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Agusa, T.; Fujihara, J.; Takeshita, H.; Iwata, H. Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms. Int. J. Mol. Sci. 2011, 12, 2351-2382. https://doi.org/10.3390/ijms12042351
Agusa T, Fujihara J, Takeshita H, Iwata H. Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms. International Journal of Molecular Sciences. 2011; 12(4):2351-2382. https://doi.org/10.3390/ijms12042351
Chicago/Turabian StyleAgusa, Tetsuro, Junko Fujihara, Haruo Takeshita, and Hisato Iwata. 2011. "Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms" International Journal of Molecular Sciences 12, no. 4: 2351-2382. https://doi.org/10.3390/ijms12042351