Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants of Beta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes

Shivani Singh; Manish Raj Kulshrestha; Anumesh K Pathak; Shetanshu Srivastava; Aditi Singh; Vandana Tiwari

doi:10.1007/s10528-023-10555-x

Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants of Beta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes

Biochem Genet. 2023 Nov 19. doi: 10.1007/s10528-023-10555-x. Online ahead of print.

Authors

Shivani Singh^{1

2}, Manish Raj Kulshrestha², Anumesh K Pathak², Shetanshu Srivastava³, Aditi Singh¹, Vandana Tiwari⁴

Affiliations

¹ Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, Uttar Pradesh, 226028, India.
² Department of Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India.
³ Department of Pediatrics, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India.
⁴ Department of Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India. drvandana2166@yahoo.com.

PMID: 37980703
DOI: 10.1007/s10528-023-10555-x

Abstract

This study investigates the genetic variations in FcεR1β-109 C/T (rs512555) and TNF-α-308 G/A (rs1800629) genes and examines whether the mosquito repellent transfluthrin (TFT) modifies the risk for asthmatic children. A case-control study was conducted involving 130 asthmatic children and 123 age-sex matched controls. Differential leukocyte counts, IgE, and hs-CRP levels were estimated using a five-part haematology analyzer and Beckman Coulter (AU480), respectively. Genetic variations in FcεR1β-109 and TNF-α-308 were analysed using restriction fragment length polymorphism. Serum TFT levels were measured using gas chromatography-tandem mass spectrometry. Asthmatic children had significantly increased total leukocyte, neutrophil, lymphocyte, eosinophil, and basophil counts (p < 0.0001), while their monocyte counts were lower compared to controls (p < 0.0001). TFT levels were higher in asthmatic children (1.38 ± 0.91 vs. control 0.69 ± 0.41µg/L, p < 0.0001), which predominantly induced wheezing. Elevated TFT levels were associated with an increased risk of childhood asthma (OR: 3.08, p < 0.0001). Children with the FcεRIβ TT (OR: 2.39, p < 0.017) and TNF-α GG genotypes (OR: 7.17, p < 0.0001) were more susceptible to asthma. TFT synergistically enhanced the risk of asthma in both FcεRIβ-109 TT (OR: 5.3, p = 0.001) and TNF-α-308 GG (OR: 17.18, p < 0.0001) genotypes. TFT levels were correlated with IgE (r = 0.363; p = 0.006), hs-CRP (r = 0.324; p = 0.049) and eosinophil (r = 0.300; p = 0.038), respectively. IgE and eosinophils were correlated (r = 0.599, p = 0.001) in the FcεRIβ TT genotype-carrying asthmatic children. Similarly, neutrophils and hs-CRP were correlated (r = 0.768, p < 0.0001) in asthmatic children with TNF-α GG genotype. The risk of asthma is inherently higher in children with FcεRIβ TT and TNF-α GG variants. TFT exposure amplifies the risk of asthma in children among all the subgenotypes of both genes. TFT influences IgE and eosinophil in FcεRIβ TT genotype while it influences neutrophils and hs-CRP in TNF-α GG genotypes.

Keywords: FcεR1β receptor; Genetic variation; IgE; TNF-α; Transfluthrin.