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Objective: This study investigates the predictive value and risk factors associated with different vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) genotypes in asthma. Methods: From December 2020 to February 2023, we studied 86 asthma patients and 70 healthy controls, analyzing VDR single nucleotide polymorphisms (SNPs) (rs1544410 and rs731236) and CaSR SNPs (rs1801726 and rs1042636) using DNA extracted from whole blood. We compared genotype distributions, demographic data, lung function parameters, vitamin D levels, and immune and inflammatory markers between the two groups. Results: The study group exhibited higher frequencies of VDR rs1544410 genotype TT and allele T, and CaSR rs1801726 genotype GG and allele G, but lower frequencies of CaSR rs1042636 genotype GG and allele G compared with controls (p < 0.05). Additionally, patients in the study group showed elevated rates of family history/genetic predisposition, allergy history, smoking, and higher levels of neutrophils, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-17, and interferon-gamma (IFN-γ ). They also demonstrated lower levels of FEV1, FVC, PEFR, and 25-(OH)-D (P < 0.05). Logistic regression identified several factors, including specific genotypes, family history, and biomarker levels, as significant asthma risk factors. Conclusion: VDR rs1544410 and CaSR rs1801726 and rs1042636 may serve as potential diagnostic markers for asthma, highlighting their role in assessing genetic predisposition and disease severity. [ABSTRACT FROM AUTHOR]