4 Journal of Toxicology Table 3: Regression coeﬃcient for blood cadmium by GSTP1 Val105Ile and interaction between GSTP1 Val105Ile and GSTT1 and GSTM1. Genotype GSTP1 Val105Ile GSTP1 Ile/Ile GSTP1 Ile/Val GSTP1 Val/Val GSTM1 and GSTP1 Val105Ile GSTM1 +/GSTP1 Ile/Ile GSTM1 +/GSTP1 Ile/Val and Val/Val GSTM1 –/GSTP1 Ile/Ile GSTM1 –/GSTP1 Ile/Val and Val/Val GSTT1 and GSTP1 Val105Ile GSTT1 +/GSTP1 Ile/Ile GSTT1 +/GSTP1 Ile/Val and Val/Val GSTT1 –/GSTP1 Ile/Ile GSTT1 –/GSTP1 Ile/Val and Val/Val n 212 139 19 96 82 126 68 121 89 108 52 Blood cadmium β (S.E.)a 0.27 (0.19) 0.35 (0.22) 0.59 (0.39) − 0.14 (0.23) 0.32 (0.26) 0.29 (0.17) 0.67 (0.46) 0.20 (0.13) 0.18 (0.21) 0.39 (0.22) 0.72 (0.58) P valueb 0.324 0.296 0.034 0.462 0.108 0.288 0.044 0.142 0.296 0.103 0.038 a Regression coeﬃcients. bP value were obtained by linear regression after controlling for sex, age, BMI, smoking status and alcohol consumption. mean of the blood cadmium concentration in a nonoccu- pationally exposed population was in the acceptable range (<5.0 μg/L) [1]. The result agreed with the previous report in Thai population [15]. Gender, age, and alcohol consumption were no inﬂu- ences on blood cadmium levels among this study population, similar to the study by Bata´riova´ et al. [16]. Cigarette smok- ing was found to be signiﬁcantly related to blood cadmi- um concentration. Smokers had signiﬁcantly higher blood cadmium concentration than nonsmokers (P < 0.05) (Table 1). It could be explained that cigarette smoking was a major source of nonoccupational cadmium exposure be- cause of cadmium in the tobacco. It had been reported that cigarettes contain cadmium in concentrations ranging from 1.56 to 1.96 μg/cigarette [17]. Blood cadmium levels ob- served in this study group appeared to be similar to those reported in the other studies [15, 16, 18, 19]. Polymorphisms in genes, which involved in metabolism of cadmium, were analyzed including GSTT1, GSTM1, and GSTP1 to explore the genetic susceptibility to cadmium tox- icity. In the present study, all tested genotype frequencies were in Hardy-Weinberg equilibrium. The GSTT1 present was the most prevalent genotype found in study population (67.3%) (Table 2). Homozygous variant of GSTP1 Val/Val was the lowest genotype in study population (5.1%). The genotypes of GSTT1 and GSTM1 were found with a frequency of 32.7%, and 57.6%, respectively, while GSTP1 Ile/Ile, Ile/Val, Val/Val genotype frequencies were 57.3%, 37.6%, and 5.1%, respectively. The similar genotype frequen- cies were reported in Thai population [20–22]. The GST gene family is involved in the detoxiﬁcation of electrophilic compounds by conjugating them with GSH and immediately excreted via the bile or urine. The level of GST expression is a crucial factor determining the sensitivity of cell to toxic chemical [23]. This gene family comprises several genes, and many of them are polymorphic in human. GSTP1 exhibits a missense mutation at codon 105, which substitutes Val to Ile. The polymorphism in GSTP1 both amino acid exchanges are in the active site of the enzyme and inﬂuence the activity toward diﬀerent substrates [24]. GSTM1 and GSTT1 exhibit deletion alleles, which eliminate enzyme activity [25]. In the present study, subjects with the GSTP1 homozygous variant (Val/Val) had signiﬁcantly higher blood cadmium level than did those with Ile/Val and wild-type (Ile/Ile) genotype. The possible explanation would be the substitution of Ile → Val in GSTP1 change catalytic activity of the corresponding GSTs [25, 26]. The change in catalytic activity may reduce in Cd-GSH conjugates and excretion, which results in cadmium accumulated in blood. Since the variation in GSTP1 genotype is associated with variation of blood cadmium concentration. Therefore, it could be assumed that GSTP1 play a more important role in variation of blood cadmium concentrations than the other investigated GST polymorphisms. With regards to gene-gene interactions, the study showed that GSTP1 Val variant allele had signiﬁcantly associated with higher blood cadmium concentration when taking into account GSTT1 or GSTM1 genotypes (Table 3). This could be explained by GST conjugated reactive com- pounds to GSH prior to their excretion from the body. The deletion of GSTT1 and GSTM1 genes reduces the catalytic activity [23], and polymorphism in GSTP1, changes catalytic activity of the corresponding GSTs [26]. Therefore, the pol- ymorphisms may aﬀect the conjugation and excretion of cadmium, which results in accumulation of this metal in blood. Moreover, not only a single genetic polymorphism of GSTs genes which may alter the enzyme activity, but also combinations of polymorphism may be more important in determining catalytic activities, expression of enzyme, and interindividual variability of disposition and response to