Lymphotoxin-α gene 252G allelic variant is a risk factor for large-vessel-associated ischemic stroke

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A direct role of lymphotoxin-α (LTA) in promoting atherosclerotic plaque growth has been demonstrated recently. The different protein transcripts of the naturally occurring genetic variants of the LTA gene have been demonstrated to exhibit affected functions, and an allelic difference in binding to transcription factor(s) has also been suggested. The homozygous variant of LTA characterized by the intron 1 252A→G (252G) transition, which naturally coexists with an exon 3 804C→A (804A) single-nucleotide polymorphism (SNP), has been reported as a susceptibility gene for myocardial infarction. Because the atherosclerotic process is also an integral component in the pathogenesis of certain types of vascular stroke, we investigated the possible significance of the above SNPs in 353 ischemic stroke patients and 180 healthy controls. The homozygous LTA allele with the 252G and 804C SNPs occurred more frequently in stroke patients (13.9%) than in controls (7.20%, p <0.025). Specific subclassification of the patients revealed an accumulation of these SNPs in large-vessel, pathology-associated cerebral infarction (18.2%); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.1 (95% confidence interval, 1.3-6.2; p <0.005). Elimination of all subjects with a history or evidence of ischemic heart disease, including myocardial infarction, did not affect this association. These data show that besides the role in the development of myocardial infarction, the homozygous carriage of the LTA allele with 252G and 804A SNPs is a novel susceptibility factor for largevesselassociated ischemic stroke.

Original languageEnglish
Pages (from-to)205-211
Number of pages7
JournalJournal of Molecular Neuroscience
Volume27
Issue number2
DOIs
Publication statusPublished - Oct 2005

Fingerprint

Lymphotoxin-alpha
Single Nucleotide Polymorphism
Genes
Stroke
Pathology
Polymorphism
Regression analysis
Introns
Myocardial Infarction
Logistics
Exons
Transcription Factors
Nucleotides
Alleles
Cerebral Infarction
Atherosclerotic Plaques
Proteins
Myocardial Ischemia
Blood Vessels
Logistic Models

Keywords

  • Genetic factor
  • Lymphotoxin-α gene
  • Risk factor
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

@article{37e0f84c3e3e4d24a451b8aad0300d10,
title = "Lymphotoxin-α gene 252G allelic variant is a risk factor for large-vessel-associated ischemic stroke",
abstract = "A direct role of lymphotoxin-α (LTA) in promoting atherosclerotic plaque growth has been demonstrated recently. The different protein transcripts of the naturally occurring genetic variants of the LTA gene have been demonstrated to exhibit affected functions, and an allelic difference in binding to transcription factor(s) has also been suggested. The homozygous variant of LTA characterized by the intron 1 252A→G (252G) transition, which naturally coexists with an exon 3 804C→A (804A) single-nucleotide polymorphism (SNP), has been reported as a susceptibility gene for myocardial infarction. Because the atherosclerotic process is also an integral component in the pathogenesis of certain types of vascular stroke, we investigated the possible significance of the above SNPs in 353 ischemic stroke patients and 180 healthy controls. The homozygous LTA allele with the 252G and 804C SNPs occurred more frequently in stroke patients (13.9{\%}) than in controls (7.20{\%}, p <0.025). Specific subclassification of the patients revealed an accumulation of these SNPs in large-vessel, pathology-associated cerebral infarction (18.2{\%}); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.1 (95{\%} confidence interval, 1.3-6.2; p <0.005). Elimination of all subjects with a history or evidence of ischemic heart disease, including myocardial infarction, did not affect this association. These data show that besides the role in the development of myocardial infarction, the homozygous carriage of the LTA allele with 252G and 804A SNPs is a novel susceptibility factor for largevesselassociated ischemic stroke.",
keywords = "Genetic factor, Lymphotoxin-α gene, Risk factor, Stroke",
author = "Zolt{\'a}n Szolnoki and Vikt{\'o}ria Havasi and G{\'a}bor Tali{\'a}n and Judit Bene and Katalin Koml{\'o}si and Ferenc Somogyv{\'a}ri and Andr{\'a}s Kondacs and Mih{\'a}ly Szab{\'o} and Lajos Fodor and Anita Bodor and B{\'e}la Melegh",
year = "2005",
month = "10",
doi = "10.1385/JMN:27:2:205",
language = "English",
volume = "27",
pages = "205--211",
journal = "Journal of Molecular Neuroscience",
issn = "0895-8696",
publisher = "Humana Press",
number = "2",

}

TY - JOUR

T1 - Lymphotoxin-α gene 252G allelic variant is a risk factor for large-vessel-associated ischemic stroke

AU - Szolnoki, Zoltán

AU - Havasi, Viktória

AU - Talián, Gábor

AU - Bene, Judit

AU - Komlósi, Katalin

AU - Somogyvári, Ferenc

AU - Kondacs, András

AU - Szabó, Mihály

AU - Fodor, Lajos

AU - Bodor, Anita

AU - Melegh, Béla

PY - 2005/10

Y1 - 2005/10

N2 - A direct role of lymphotoxin-α (LTA) in promoting atherosclerotic plaque growth has been demonstrated recently. The different protein transcripts of the naturally occurring genetic variants of the LTA gene have been demonstrated to exhibit affected functions, and an allelic difference in binding to transcription factor(s) has also been suggested. The homozygous variant of LTA characterized by the intron 1 252A→G (252G) transition, which naturally coexists with an exon 3 804C→A (804A) single-nucleotide polymorphism (SNP), has been reported as a susceptibility gene for myocardial infarction. Because the atherosclerotic process is also an integral component in the pathogenesis of certain types of vascular stroke, we investigated the possible significance of the above SNPs in 353 ischemic stroke patients and 180 healthy controls. The homozygous LTA allele with the 252G and 804C SNPs occurred more frequently in stroke patients (13.9%) than in controls (7.20%, p <0.025). Specific subclassification of the patients revealed an accumulation of these SNPs in large-vessel, pathology-associated cerebral infarction (18.2%); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.1 (95% confidence interval, 1.3-6.2; p <0.005). Elimination of all subjects with a history or evidence of ischemic heart disease, including myocardial infarction, did not affect this association. These data show that besides the role in the development of myocardial infarction, the homozygous carriage of the LTA allele with 252G and 804A SNPs is a novel susceptibility factor for largevesselassociated ischemic stroke.

AB - A direct role of lymphotoxin-α (LTA) in promoting atherosclerotic plaque growth has been demonstrated recently. The different protein transcripts of the naturally occurring genetic variants of the LTA gene have been demonstrated to exhibit affected functions, and an allelic difference in binding to transcription factor(s) has also been suggested. The homozygous variant of LTA characterized by the intron 1 252A→G (252G) transition, which naturally coexists with an exon 3 804C→A (804A) single-nucleotide polymorphism (SNP), has been reported as a susceptibility gene for myocardial infarction. Because the atherosclerotic process is also an integral component in the pathogenesis of certain types of vascular stroke, we investigated the possible significance of the above SNPs in 353 ischemic stroke patients and 180 healthy controls. The homozygous LTA allele with the 252G and 804C SNPs occurred more frequently in stroke patients (13.9%) than in controls (7.20%, p <0.025). Specific subclassification of the patients revealed an accumulation of these SNPs in large-vessel, pathology-associated cerebral infarction (18.2%); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.1 (95% confidence interval, 1.3-6.2; p <0.005). Elimination of all subjects with a history or evidence of ischemic heart disease, including myocardial infarction, did not affect this association. These data show that besides the role in the development of myocardial infarction, the homozygous carriage of the LTA allele with 252G and 804A SNPs is a novel susceptibility factor for largevesselassociated ischemic stroke.

KW - Genetic factor

KW - Lymphotoxin-α gene

KW - Risk factor

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=25144486062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25144486062&partnerID=8YFLogxK

U2 - 10.1385/JMN:27:2:205

DO - 10.1385/JMN:27:2:205

M3 - Article

C2 - 16186631

AN - SCOPUS:25144486062

VL - 27

SP - 205

EP - 211

JO - Journal of Molecular Neuroscience

JF - Journal of Molecular Neuroscience

SN - 0895-8696

IS - 2

ER -