Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in IndiaCitation formats

  • External authors:
  • Stuti Mohanty
  • Sanjib Mohanty
  • Aparup Das
  • Veena Pande
  • Akshaya Kumar Mohanty

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Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India. / Mohanty, Stuti; Mohanty, Sanjib; Das, Aparup; Pande, Veena; Singh, Upasana Shyamsunder; Mohanty, Akshaya Kumar.

In: Infection, Genetics and Evolution, Vol. 69, 2019, p. 107-116.

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Mohanty, Stuti ; Mohanty, Sanjib ; Das, Aparup ; Pande, Veena ; Singh, Upasana Shyamsunder ; Mohanty, Akshaya Kumar. / Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India. In: Infection, Genetics and Evolution. 2019 ; Vol. 69. pp. 107-116.

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@article{2c5e202f768e47a59d06a1a952b6d9c0,
title = "Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India",
abstract = "Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (−1031 T > C, −863C > A, −857C > T, −308G > A, −806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the −1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India.",
keywords = "Malaria, Cerebral malaria, TNF-αSNPPromoter",
author = "Stuti Mohanty and Sanjib Mohanty and Aparup Das and Veena Pande and Singh, {Upasana Shyamsunder} and Mohanty, {Akshaya Kumar}",
year = "2019",
doi = "10.1016/j.meegid.2019.01.025",
language = "English",
volume = "69",
pages = "107--116",
journal = "Infection, Genetics and Evolution",
issn = "1567-1348",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India

AU - Mohanty, Stuti

AU - Mohanty, Sanjib

AU - Das, Aparup

AU - Pande, Veena

AU - Singh, Upasana Shyamsunder

AU - Mohanty, Akshaya Kumar

PY - 2019

Y1 - 2019

N2 - Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (−1031 T > C, −863C > A, −857C > T, −308G > A, −806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the −1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India.

AB - Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (−1031 T > C, −863C > A, −857C > T, −308G > A, −806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the −1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India.

KW - Malaria

KW - Cerebral malaria

KW - TNF-αSNPPromoter

U2 - 10.1016/j.meegid.2019.01.025

DO - 10.1016/j.meegid.2019.01.025

M3 - Article

VL - 69

SP - 107

EP - 116

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

SN - 1567-1348

ER -