RESUMO
Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. The objective of this study was to investigate the diversity of the AS3MT gene in Mexican and German populations. The distribution of 18 single nucleotide polymorphisms (SNPs) in AS3MT was assessed on healthy individuals: 38 Mestizo, 69 Nahuas, 50 Huicholes, and 32 Germans. All 18 SNPs were polymorphic in the German and Mexican populations. Of the three Mexican populations, a minor allele frequency was the highest in the Mestizo, followed by the Nahuas and Huicholes. In the German and three Mexican groups, haplotype #1(TATAGAAGTCTTCATGAC) was the most predominant. Seven haplotypes were newly found in the German and three Mexican populations. The D' values between SNP pairs were high in the German and Nahua populations; they had a similar pattern. The pattern of the Mestizo was more similar to the African than to the other Mexican populations. Huicholes had a moderate pattern of the African and German/Nahua populations. The network had three clusters. One originated in the African population and another may have originated in an Asian (Chinese and/or Japanese) population. The third one may have originated among Caucasians. This study is the first to demonstrate the existence of genetic heterogeneity in the distribution of 18 SNPs in AS3MT of German and Mexican populations.
Assuntos
Arsênio/metabolismo , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Arsênio/toxicidade , Feminino , Frequência do Gene , Alemanha , Haplótipos , Humanos , Indígenas Norte-Americanos/genética , Desequilíbrio de Ligação , Masculino , México , População Branca/genéticaRESUMO
Delta-aminolevulinic acid dehydratase (ALAD) is a cytosolic enzyme in the heme biosynthetic pathway. The ALAD is controlled by two codominant alleles (ALAD1 and ALAD2), which result in a Asn-Lys substitution at amino acid position 59 of the mature enzyme based on a single nucleotide polymorphism (SNP) (G177C) leading three phenotypes (ALAD1-1, ALAD1-2, and ALAD2-2). Previous studies have shown that this polymorphism is related to lead toxicity. There is little evidence showing interethnic differences in the distribution of this polymorphism. We examined the distribution of genetic variants of the ALAD G177C polymorphism in four Asians, three Africans, and three Mexicans. Genomic DNA was extracted from blood or bloodstain, and the genotypes for the ALAD polymorphism were determined by PCR followed by RFLP digestion and gel electrophoresis. We found a notable interethnic disparity in the distribution of ALAD G177C genotypes and alleles. The frequencies of ALAD2 in Asian populations were comparable to those in Caucasians, while Africans had no mutation allele. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity.