Allelic Association and Functional Studies of Promoter Polymorphism in the Leukotriene C4 Synthase Gene (LTC4S) in Asthma

Overview

Journal Thorax

Date 2003 May 3

PMID 12728163

Citations 13

Authors

I Sayers

S Barton

S Rorke

B Beghe

B Hayward

P Van Eerdewegh

T Keith

J B Clough

S Ye

J W Holloway

A P Sampson

S T Holgate

Affiliations

Soon will be listed here.

Abstract

Background: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 (A/C) polymorphism has previously been reported. The role of these polymorphisms in the genetic susceptibility to asthma was examined.

Methods: To test for genetic association with asthma phenotypes, 341 white families (two asthmatic siblings) and 184 non-asthmatic control subjects were genotyped. Genetic association was assessed using case control and transmission disequilibrium test (TDT) analyses. LTC4S promoter luciferase constructs and transiently transfected human HeLa and KU812F cells were generated to determine the functional role of these polymorphisms on basal transcription.

Results: No associations were observed in case control analyses (-1072 A, q=0.09; -444 C, q=0.29); the TDT identified a borderline association between the -444 C allele and bronchial responsiveness to methacholine (p=0.065). Asthmatic children with the -444 C allele had a lower mean basal forced expiratory volume in 1 second (97.4 v 92.7% predicted, p=0.005). LTC4S promoter luciferase analyses provided no evidence for a functional role of either polymorphism in determining basal transcription.

Conclusion: This study does not support a role for these polymorphisms in genetic susceptibility to asthma but provides evidence to suggest a role in determining lung function parameters.

Citing Articles

Hyper-methylation and DNMT3A mediated LTC4S downregulation promoted lung adenocarcinoma tumorigenesis via mTORC1 signaling pathway.

Ren Y, Zhang P, Li L, Wang M, Hu H, Shen Y Heliyon. 2024; 10(13):e33203.

PMID: 39027522 PMC: 11255598. DOI: 10.1016/j.heliyon.2024.e33203.

Correlation between LTC4S -444 A>C polymorphism and susceptibility to asthma: A meta-analysis and trial sequential analysis.

Wu D, Liu Y, Liu Y, Cui N, Zhu Y, Zheng S J Med Biochem. 2024; 43(1):106-115.

PMID: 38496016 PMC: 10943467. DOI: 10.5937/jomb0-44538.

New Insights on the Role of pentraxin-3 in Allergic Asthma.

Koussih L, Atoui S, Tliba O, Gounni A Front Allergy. 2022; 2:678023.

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Potential Metabolic Biomarkers in Adult Asthmatics.

Sim S, Choi Y, Park H Metabolites. 2021; 11(7).

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Association of Leukotriene C4 Synthase A-444C Polymorphism with Asthma and Asthma Phenotypes in Romanian Population.

Berghea E, Popa L, Dutescu M, Meirosu M, Farcasanu I, Berghea F Maedica (Bucur). 2017; 10(2):91-96.

PMID: 28275397 PMC: 5327799.

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