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Possible Positive Selection for an Arsenic-Protective Haplotype in Humans

Schlebusch, Carina M. ; Lewis, Cecil M. Jr. ; Vahter, Marie ; Engström, Karin LU ; Tito, Raul Y. ; Obregon-Tito, Alexandra J. ; Huerta, Doris ; Polo, Susan I. ; Medina, Angel C. and Brutsaert, Tom D. , et al. (2013) In Environmental Health Perspectives 121(1). p.53-58
Abstract
BACKGROUND: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite. OBJECTIVES: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. METHODS: Indigenous groups we evaluated were a)... (More)
BACKGROUND: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite. OBJECTIVES: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. METHODS: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic. RESULTS: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide micro-satellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation F-ST = 0.006) and low levels of structure between SAC and HGDP populations (F-ST < 0.055 for all pairs of populations compared). CONCLUSIONS: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AS3MT, dimethylarsinic acid, DMA, drinking water, Human Genome Diversity, Project, methylarsonic acid, MMA
in
Environmental Health Perspectives
volume
121
issue
1
pages
53 - 58
publisher
National Institute of Environmental Health Sciences
external identifiers
  • wos:000323698700024
  • scopus:84872084310
  • pmid:23070617
ISSN
1552-9924
DOI
10.1289/ehp.1205504
language
English
LU publication?
yes
id
4c1eae31-81ce-4efa-b2f8-d9615415d1a5 (old id 4062591)
date added to LUP
2016-04-01 13:04:30
date last changed
2022-03-06 03:39:36
@article{4c1eae31-81ce-4efa-b2f8-d9615415d1a5,
  abstract     = {{BACKGROUND: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite. OBJECTIVES: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. METHODS: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic. RESULTS: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p &lt; 0.001, Fisher exact test) and Peruvian (50.5%, p &lt; 0.001) populations. Genome-wide micro-satellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation F-ST = 0.006) and low levels of structure between SAC and HGDP populations (F-ST &lt; 0.055 for all pairs of populations compared). CONCLUSIONS: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.}},
  author       = {{Schlebusch, Carina M. and Lewis, Cecil M. Jr. and Vahter, Marie and Engström, Karin and Tito, Raul Y. and Obregon-Tito, Alexandra J. and Huerta, Doris and Polo, Susan I. and Medina, Angel C. and Brutsaert, Tom D. and Concha, Gabriela and Jakobsson, Mattias and Broberg Palmgren, Karin}},
  issn         = {{1552-9924}},
  keywords     = {{AS3MT; dimethylarsinic acid; DMA; drinking water; Human Genome Diversity; Project; methylarsonic acid; MMA}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{53--58}},
  publisher    = {{National Institute of Environmental Health Sciences}},
  series       = {{Environmental Health Perspectives}},
  title        = {{Possible Positive Selection for an Arsenic-Protective Haplotype in Humans}},
  url          = {{https://lup.lub.lu.se/search/files/3145102/4882619.pdf}},
  doi          = {{10.1289/ehp.1205504}},
  volume       = {{121}},
  year         = {{2013}},
}