A coding variant (rs4925) at GSTO1
and an upstream variant (rs2297235) at GSTO2 were associated with PC1.
Other SNPs in genes involved in inflammation (APOE and IL6), oxidative stress (NOS3 and SOD2), and As metabolism (AS3MT, CBS, GSTO1
, and MTHFR) showed nominally significant interactions with well-water As for associations with CVD, CHD, or stroke.
KEY WORDS: arsenic, AS3MT, blood, GSTO1, methylation, MTHFR, polymorphisms, sex, urine.
One arsenic-reductase has been identified to be glutathione-S-transferase omega (GSTO1), which is able to reduce both MA(V) to MA(III) and arsenate [As(V)] to arsenite [As(III)] (Zakharyan et al.
Hs.214142; National Center for Biotechnology Information 2007), GSTO1 (Hs.190028), and AS3MT (Hs.34492).
The allele and genotype frequencies for the A222V (C[right arrow]T) MTHFR, E429A (A[right arrow]C) MTHFR, A140D (C[right arrow]A) GSTO1, and M287T (T[right arrow]C) AS3MT polymorphisms are shown in Table 2.
Table 3 shows the results of the multiple regression analyses to test whether the distributions of urinary arsenic metabolites were dependent on sex, age, BMI, selenium, and gene polymorphisms in MTHFR, GSTO1, and AS3MT.
Recent findings from small-scale studies indicate that polymorphisms in glutathione S-transferase (GST) omega 1 (GSTO1), which encodes an enzyme that can reduce pentavalent As species, might be related to enzyme activity and patterns of methylated As metabolites (Marnell et al.
The genes of interest were selected by a) searching for new and previously reported polymorphisms in GSTO1 and AS3MT by sequencing; and b) screening for previously reported polymorphisms in GSTM1, GSTT1, GSTO1, MTR, and MTHFR.
Furthermore, samples taken year 2004 were genotyped for Glu155del (deletion of glutamate 155) and Thr217Asn in GSTO1 with RFLP.
For GSTO1, we found no polymorphisms with an allele frequency > 20%.
For GSTO1, the frequencies of polymorphisms were far too low to affect the distribution of urinary As metabolites among the population.