Efficiency of methylated process was assessed by calculating
Efficiency of methylated process was assessed by calculating PMI and SMI. On average, PMI was 0.9 and ranged from 0.1 to 3.8 while SMI was 4.9 and ranged from 0.3 to 21.3. The observed differences in the arsenic methylation can be associated with the inter-individual variations caused by a genetic polymorphism in the methylation of arsenic. This variability may be also attributed by factors such as lifestyle, dietary, nutritional, sex, age and BMI (Tseng, 2009). Regarding the prevalence of GST polymorphic, GSTT1 and GSTM1 variants were similar to those reported for other Latin-American studies (Marcos et al., 2006; Caceres et al., 2010). GSTP1-val/val polymorphic variant has also been reported in populations with a high prevalence of different ethnic groups (Ramprasath et al., 2011; Lesseur et al., 2012). Likewise, MT-2A polymorphic variants prevalence has been evaluated in some studies in Turkish (Kayaalti and Soylemezoglu, 2010), Polish (Forma et al., 2012) and Japanese populations (Kita et al., 2006) but we found very low prevalence in our study. According to the analysis of the effects of these polymorphisms on the PUAS, the results of logistic regression analysis showed significant associations between %InAs as dependent variable, GSTP1 polymorphism and LADD of Arsenic as exposure variable. Also, the models were adjusted by potential confounders such as age, BMI, and alcohol consumption, and the factors studied explain 43% of all the variation of InAs (p = 0.000). Other outcome showed significant associations between PMI as dependent variable and GSTP1 and GSTM1 polymorphism as exposure variable, when the models were adjusted by potential confounders such as sex, BMI, and alcohol consumption, was observed a poor statistical strength (R2 = 0.20; p = 0.007). However, it has been reported that a combined GSTP1 and GSTM1-null A 804598 resulted in signiﬁcantly reduced GST activity (Zhong et al., 2006). Therefore, also is probable that a combination of GSTP1 and GSTM1-null could affect As metabolism (Agusa et al., 2010; Lesseur et al., 2012), but new evidence is needed. The effect of GSTP1 on As metabolic capacity has been reported previously in the literature. Some studies in Chilean populations found greater DMA excretion in the GSTP1-val/val type individuals, but it was not significant (Marcos et al., 2006). On the other hand, it was found in Vietnam that the heterozygote of GSTP1 Ile/Val type had a higher metabolic capacity from InAs to MMA, clarifying that GSTP1 has no function of As methylation (Agusa et al., 2010). The same authors suggest in another study that the heterozygote of GSTP1 Ile105Val might have a lower reduction capacity from AsV to AsIII, but the metabolism to MMAV may be more facilitated. Also heterozygote of GSTP1 Ile105Val type had higher PMI than the GSTP1 Ile/Ile wild type (Agusa et al., 2012). Although, in our study only was observed association statistically significant among GSTP1 and InAs (p = 0.007) and GSTP1 with PMI, (p = 0.002), the finding are opposites according to GSTP1 type variant of risk on excretion of urinary As metabolites. AsIII and AsV were greater in the GSTP1 AA (Ile/Ile) wild type compared with heterozygote of AG (Ile/Val) type and homozygote of GG (Val/Val) type (combinations by dominant model). Further, AA (Ile/Ile) wild type had higher PMI than the heterozygote of AG (Ile/Val) type and homozygote of GG (Val/Val) type (p = 0.002). The mechanism of this effect involves the activity of glutathione. This is responsible of the arsenic metabolic regulation via GST polymorphisms. As consequence of low activity of the GST by polymorphisms, is possible decrease the detoxification function of glutathione, altering the PUAS. Further, this effect may be accelerated with an increase on arsenic exposure dosage, which was observed in the present study. To elucidate these finding, is need develop new studies that including all the genotypes involved in As metabolism as well as the As exposure dosage and their potential interactions.