Evaluation of ADAM33 gene's single nucleotide polymorphism variants against asthma and the unique pattern of inheritance in Northern and Central Punjab, Pakistan.

OBJECTIVES: To investigate the relationship of 3 single nucleotide polymorphism (SNP) variants of ADAM33 with asthma susceptibility in patients from Northern and Central Punjab, Punjab, Pakistan. Methods: In this case-control study, healthy and asthmatic participants were recruited between 2015 and 2017. The SNPs of ADAM33 gene, rs2280089, rs2280090, and rs2280091 were analyzed in 296 asthma patients and 343 healthy controls, as well as linkage disequilibrium and haplotype analysis. RESULTS: The non-significant differences were observed in allele and genotype frequencies of the SNPs in asthmatic and healthy persons even after population stratification based on age, caste, gender, family history, and environment. Although these SNPs were non-significant for disease susceptibility among children and adults, a fixed unique pattern of inheritance was nevertheless observed for the studied SNPs. Linkage disequilibrium analysis presented a very strong linkage between the SNP variants to predict their co-inheritance in study population. However, none of the haplotypes were found to be associated with asthma disease development. CONCLUSION: The studied SNPs of ADAM33 appeared to be non-significant for asthma susceptibility in  Northern and Central Punjabi population. The fixed allele combination inheritance pattern was a unique observation contrary to findings in other global populations.

PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.

Recessive splice site and nonsense mutations of PCDH15, encoding protocadherin 15, are known to cause deafness and retinitis pigmentosa in Usher syndrome type 1F (USH1F). Here we report that non-syndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. This suggests a genotype-phenotype correlation in which hypomorphic alleles cause non-syndromic hearing loss, while more severe mutations of this gene result in USH1F. We localized protocadherin 15 to inner ear hair cell stereocilia, and to retinal photoreceptors by immunocytochemistry. Our results further strengthen the importance of protocadherin 15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function.