Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in Native Paraguayans

Alicia K. Wilbur, Laura Salter Kubatko, Ana Hurtado, Kim Hill, Anne Stone

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Aché and the Avá. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Aché, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalTuberculosis
Volume87
Issue number4
DOIs
StatePublished - Jul 2007

Fingerprint

Calcitriol Receptors
vitamin D
tuberculosis
Tuberculosis
genetic polymorphism
receptors
Genes
North American Indians
genes
Population
Alleles
alleles
Infection
infection
delayed hypersensitivity
American Indians
Homozygote
Delayed Hypersensitivity
Adaptive Immunity
homozygosity

Keywords

  • Aché
  • Native Americans
  • South America
  • Tuberculosis
  • Vitamin D receptor

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Microbiology
  • Immunology and Allergy
  • Infectious Diseases
  • veterinary(all)

Cite this

Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in Native Paraguayans. / Wilbur, Alicia K.; Salter Kubatko, Laura; Hurtado, Ana; Hill, Kim; Stone, Anne.

In: Tuberculosis, Vol. 87, No. 4, 07.2007, p. 329-337.

Research output: Contribution to journalArticle

@article{9a4f57d367da4775ae6d5666ef22446b,
title = "Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in Native Paraguayans",
abstract = "Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Ach{\'e} and the Av{\'a}. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Ach{\'e}, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.",
keywords = "Ach{\'e}, Native Americans, South America, Tuberculosis, Vitamin D receptor",
author = "Wilbur, {Alicia K.} and {Salter Kubatko}, Laura and Ana Hurtado and Kim Hill and Anne Stone",
year = "2007",
month = "7",
doi = "10.1016/j.tube.2007.01.001",
language = "English (US)",
volume = "87",
pages = "329--337",
journal = "Tuberculosis",
issn = "1472-9792",
publisher = "Churchill Livingstone",
number = "4",

}

TY - JOUR

T1 - Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in Native Paraguayans

AU - Wilbur, Alicia K.

AU - Salter Kubatko, Laura

AU - Hurtado, Ana

AU - Hill, Kim

AU - Stone, Anne

PY - 2007/7

Y1 - 2007/7

N2 - Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Aché and the Avá. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Aché, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.

AB - Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Aché and the Avá. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Aché, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.

KW - Aché

KW - Native Americans

KW - South America

KW - Tuberculosis

KW - Vitamin D receptor

UR - http://www.scopus.com/inward/record.url?scp=34250647365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250647365&partnerID=8YFLogxK

U2 - 10.1016/j.tube.2007.01.001

DO - 10.1016/j.tube.2007.01.001

M3 - Article

C2 - 17337247

AN - SCOPUS:34250647365

VL - 87

SP - 329

EP - 337

JO - Tuberculosis

JF - Tuberculosis

SN - 1472-9792

IS - 4

ER -