The Effect of Genetic Admixture in an Association Study: Genetic Polymorphisms and Chromosome Aberrations in a Colombian Population Exposed to Organic Solvents

Abstract

SummaryThe human population is heterogeneous in genetic susceptibility, chromosomal instability and disease risk; all factors which depend on inherited genetic constitution and acquired nongenetic environmental and occupational factors. Recently, special attention has been directed to the identification of sources of potential bias in population studies of gene-environment interactions including genetic admixture. The aim of this study was to evaluate the effect of genetic admixture in the association of genetic polymorphisms and chromosome aberrations (CA) in a population exposed to organic solvents. We assessed genetic admixture via 34 genetic ancestry informative markers (AIMs) in 398 Colombian individuals. We report a statistically significant difference of higher CA frequency in individuals' below-average European component, and in individuals' above-average Native American component after adjusting for covariates. In addition, the confounding risk ratio values are ≥10% than the adjusted risk ratio, suggesting that population stratification is a confounding factor in this gene-environment association study. Furthermore, after adjusting for individual admixture proportions and covariates, the results demonstrate that glutathione-S-transferase M1 (GSTM1)-null is associated with CA frequency increase. These results suggest that gene-environment association studies that involve recently admixed populations should take into consideration population stratification as a confounding factor and suggest GSTM1-null as a genetic marker associated with CA frequency increase.

Metabolic gene variants associated with chromosomal aberrations in healthy humans

“…The effects of smoking and occupational exposures would be expected to be mediated by genotoxic substances and many of these are subject to metabolic conversion through type 1 and 2 enzyme systems before excretion. There is ample literature on this theme (Au et al, ; Knudsen et al, ; Vodicka et al, ; Cajas‐Salazar et al, ; Hoyos‐Giraldo et al, ; Musak et al, ). The present dataset offers an attractive possibility to address interactions between occupational exposures or smoking status and genotypes.…”

Gene-specific promoter methylation is associated with micronuclei frequency in urothelial cells from individuals exposed to organic solvents and paints

“…18,19 Details of the study population and organic solvents and paint exposure have been described previously. 18 Briefly, 150 car painters were recruited from several workshops from the southwest of Colombia.…”

Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos

“…Se determinó que, a diferencia de otros estudios(4,36,37), la frecuencia de MNs no incrementa con la ausencia de GSTM1 o GSTT1 en el grupo expuesto o referente. Estas diferencias en los resultados pueden ser atribuidas a otros factores genéticos de confusión, como la mezcla ancestral de estos individuos, basado en un anterior reporte(38). Es importante mencionar que estas diferencias en los resultados no son atribuibles a un bajo poder en la muestra de individuos evaluados.…”