| Autor: |
Vishweswaraiah S; Department of Studies in Genetics and Genomics, University of Mysore, Manasagangotri, Mysore 570006, India., Ramachandra NB; Department of Studies in Genetics and Genomics, University of Mysore, Manasagangotri, Mysore 570006, India., Joshi N; Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India., Parthasarathi A; Allergy, Asthma and Chest Centre, Krishnamurthypuram, Mysore 570004, India.; Rutgers Centre for Pharmacoepidemiology and Treatment Science, New Brunswick, NJ 08901-1293, USA., Kaleem Ullah M; Centre for Excellence in Molecular Biology and Regenerative Medicine (A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India.; Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, CA 94720, USA., Siddaiah JB; Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India., Holla AD; Allergy, Asthma and Chest Centre, Krishnamurthypuram, Mysore 570004, India., Chakraborty S; Center of Excellence, Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics & Integrative Biology, AcSIR (Academy of Scientific and Innovative Research), Delhi 110025, India., Agrawal A; Center of Excellence, Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics & Integrative Biology, AcSIR (Academy of Scientific and Innovative Research), Delhi 110025, India., Mahesh PA; Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India. |
| Abstrakt: |
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. |
