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. 2023 Jan 22;13(3):405.
doi: 10.3390/diagnostics13030405.

Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma

Sangeetha Vishweswaraiah  1 , Nallur B Ramachandra  1 , Neha Joshi  2 , Ashwaghosha Parthasarathi  3   4 , Mohammed Kaleem Ullah  5   6 , Jayaraj Biligere Siddaiah  2 , Amrutha D Holla  3 , Samarpana Chakraborty  7 , Anurag Agrawal  7 , Padukudru Anand Mahesh  2
Affiliations

Association between ADAM33 Single-Nucleotide Polymorphisms and Treatment Response to Inhaled Corticosteroids and a Long-Acting Beta-Agonist in Asthma

Sangeetha Vishweswaraiah et al. Diagnostics (Basel). .

Abstract

ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case-control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population.

Keywords: ADAM33; ICS; LABA; SNP; asthma; polymorphism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The haplotype block of ADAM33 SNPs rs2853209 and rs3918396 was significantly associated with asthma. Color gradient description: The red blocks indicate strong linkage disequilibrium and white blocks indicate low linkage disequilibrium.
Figure 2
Figure 2
Forest plot of ADAM33 SNPs genotypes rs2280091, rs2787094, rs3918396, rs677044, rs2853209, rs3918392 and their association with asthma according to various studies conducted globally [56,59,60,61,62,63,64,65,66,67,68].
See this image and copyright information in PMC

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