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. Author manuscript; available in PMC: 2014 Apr 7.
Published in final edited form as: Sci Total Environ. 2011 Nov 26;429:76–91. doi: 10.1016/j.scitotenv.2011.08.051

Table 2.

Studies describing genetic susceptibility in relation to arsenic-induced adverse health outcomes

Reference County Design Characteristics of subjects Main Findings
Loffredo et al. (2003) Mexico Cross-sectional 180 and 112 individuals exposed to high
and low water As (408 (µg/L and 30 (µg/L)		 Gender differences varied by populations. Bimodal
distributions were observed in the ratios of DMA to InAs and
to MMA. The results of studies among the ethnic groups in
this study are consistent with the presence of functional
genetic polymorphisms in As methylation leading to
measurable differences in toxicity.
Del Razo et al. (1997) Mexico Cross-sectional 35 and 34 exposed to high and low water As
(0.408 mg/L and 0.031 mg/L)		 Significant increases in the relative proportions of InAs and
MMA, accompanied by decreases of DMA were found in
exposed individuals.
Chung et al. (2002) Chile Cross-sectional 11 families with high drinking water As
(735–762 µg/L)		 Methylation patterns aggregate in families and are correlated
in siblings, providing evidence of a genetic basis for the
variation in arsenic methylation.
Hopenhayn-Rich et al. (1996) Chile Cross-sectional 73 individuals drinking water with As 600
µg/L and intervened with low water As (45
µ/L) for two months		 Decrease in As exposure associated with a small decrease in
In-As in urine as well as a decrease in the MMA/DMA ratio.
Study observed about 20% of the interindividual variability.
Genetic polymorphisms in As-methylating enzymes/cofactors
likely contribute to a large portion of the remaining
variability.
Hopenhayn-Rich et al. (1996) Chile Cross-sectional 122 high-exposure individuals (drinking
water: 600 µg As/L), 98 low-exposure
individuals (drinking water: 15 µg As/L)		 MMA:DMA was 1.5 times greater in exposed group.
Differences in MMA:DMA were partially (30%) explained
through exposure, smoking, and gender.
Engstrom et al. (2007) Argentina Cross-sectional 147 women drinking water As 200 µg/L Polymorphisms in AS3MT - and possibly GSTM1, GSTT1,
MTR and MTHFR - are responsible for a large part of the
interindividual variation in As metabolism and susceptibility.
Meza et al. (2007) Mexico Cross-sectional 135 individuals exposed to water As
between 5.5 µg/L and 43.3 µgL		 AS3MT individuals may suffer less risk from As exposure
than non-variant individuals. Regardless of AS3MT variant
status, children tend to have lower %MMA values than adults.
Engstrom et al. (2009) Argentina Cross-sectional
Cross-sectional		 104 women drinking water 200 µg/L As Polymorphisms in AS3MT and in genes involved in one-carbon metabolism and reduction reactions affects As
metabolism.
Gomez-Rubio et al. (2010) Mexico Cross-sectional 405 individuals Genetic association analysis with As metabolism confirmed
the previously observed association between AS3MT
variats, including a large cluster of linked polymorphisms,
and As methylation efficiency.
Paiva et al. (2008) Chile Cross-sectional 281 (urinary As: 0–600 mg/L Heterozygotes inheriting the Val236 variant subunit would likely have a partial deficiency of GSTOl-1 (glutathione transferase omega 1) activity. Despite their effects on enzyme function, the known variants of GSTOl-1 do not appear to explain the observed variability in the excretion of inorganic arsenic.
Sampayo-Reyes et al. (2010) Mexico Cross-sectional 124 high-exposure individuals A positive association was found between the level of
exposure and the genetic damage (p < 0.001). AS3MT Met287Thr was found to significantly influence the effect among children carrying the 287Thr variant allele.
Marnell et al. (2003) Mexico Cross-sectional 75 individuals living in cities with varying
As in drinking water: 9, 17, 52, and 100
µg/L		 Polymorphisms in the gene for MM A reductase/hGSTOl may be one of the reasons for the large interindividual variability in the response of humans to chronic As exposure.
Marcos et al. (2006) Chile Cross-sectional 105 smelting plant workers, 52 plant administrators, and 50 workers from
another copper mine with no significant exposure		 High amounts of inorganic As and MMA were observed in
the most exposed workers compared to the least-exposed workers who excreted high amounts of DMA. A tendency
was observed between GSTM1 null and MMA excretion, as well as between GSTP1 val/val and DMA excretion.
Steinmaus et al. (2007) Argentina Cross-sectional 170 individuals from arsenic-exposed
region		 This study provides evidence that MTHFR and GSTM1 are involved in As metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.
Engstrom et al. (2010) Argentina Cross-sectional 108 women drinking water with 200 µg/L The strongest association was found between %MMA and 8-oxo-G Inconsistencies between As and 8-oxodG stressed population variations in As metabolism.