Open Access Research Report
Salah Hashim Shaheed1,2
, Hadi Sajid Abdulabbas3, Yasir Haider Al-Mawlah4,*, Yusor Fadhil Alasadi5
1College of Applied Medical Sciences, University of Kerbala, Kerbala, Iraq
2Department of Medical Laboratory Technique, Al-Safwa University College, Kerbala, Iraq
3Department of Biology, College of Sciences, University of Babylon, Hillah, Babylon, Iraq
4DNA Research Center, University of Babylon, Hillah, Babylon, Iraq
5Department of Radiology and Nuclear Medicine Techniques, College of Advanced Technologies, University of Warith Al-Anbiyaa, Kerbala, Iraq
*Corresponding author
Yasir Haider Al-Mawlah, DNA Research Center, University of Babylon, Babylon City, Iraq;
email: yasser.almawla@uobabylon.edu.iq
Published: 13 July 2026; https://doi.org/10.61873/FERS3239
Abstract
Background: Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by abnormal secretion of parathyroid hormone (PTH) and a broad spectrum of clinical manifestations. Genetic polymorphisms in the calcium-sensing receptor (CASR) gene, especially in regulatory regions, might influence the risk and severity of the disease. Aim: This study aimed to investigate the association between a 5′-untranslated region (5′-UTR) polymorphism of the CASR gene and PHPT, and to evaluate its relationship with key biochemical and renal parameters. Methodology: In this case–control study, 60 patients with PHPT and 60 healthy controls were enrolled. Serum biochemical markers, including PTH, albumin-corrected calcium, phosphate, vitamin D, alkaline phosphatase (ALP), creatinine, and estimated glomerular filtration rate (eGFR), were measured. The 5′-UTR polymorphism of the CASR gene was analyzed using PCR–single-strand conformation polymorphism (PCR-SSCP), followed by confirmatory DNA sequencing. Associations between SSCP haplotypes and clinical parameters were assessed statistically. Results: PHPT patients exhibited significantly higher serum PTH levels (145.5 ± 40.1 vs. 32.8 ± 10.5 pg/mL, p<0.001), lower vitamin D levels (18.5 ± 5.5 vs. 35.2 ± 8.8 ng/mL, p<0.001), and elevated ALP levels (p<0.01) compared with controls. Renal dysfunction was evident in patients, with significantly higher serum creatinine and lower eGFR (p<0.05), despite the absence of significant hypercalcemia. PCR-SSCP analysis identified two distinct haplotypes (two-band and three-band patterns). The three-band variant was significantly more frequent in PHPT patients than in controls (25.0% vs. 8.3%; p=0.019; OR = 3.6, 95% CI: 1.2–11.4). Sequencing revealed a regulatory A>G substitution (rs7652589) at position 117 in the 5′-UTR of CASR. Among PHPT patients, the three-band variant was associated with higher creatinine levels and lower eGFR (p<0.05), suggesting more pronounced renal impairment, while ALP showed a borderline increase (p=0.051). Conclusion: A polymorphic variant in the 5′-UTR of the CASR gene is significantly associated with PHPT and may contribute to disease susceptibility and renal dysfunction. This regulatory variant might influence CASR expression and calcium homeostasis, suggesting a possible role for non-coding genetic variation in the pathophysiology and clinical heterogeneity of PHPT.
Keywords: primary hyperparathyroidism, calcium-sensing receptor, CASR, 5′-UTR polymorphism, PCR-SSCP, renal function
Please cite as:
Shaheed S. H., Abdulabbas H. S., Al-Mawlah Y. H., Alasadi Y. F.: Association of a 5′-untranslated region polymorphism in the CASR gene with primary hyperparathyroidism and renal dysfunction. Epitheorese Klin. Farmakol. Farmakokinet. 44: 1-10 (2026). DOI: 10.61873/FERS3239
pISSN 1011-6575 • eISSN 2945-1914