Receptor gene expressions and their association with biochemical parameters in primary hyperparathyroidism patients

Abstract

Aims: Primary hyperparathyroidism (PHPT) is recognized by excessive parathyroid hormone (PTH) secretion, leading to hypercalcemia and systemic complications. This study aimed to investigate the gene expression profiles of PTH, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), fibroblast growth factor receptor 1 (FGFR1), and α-Klotho from parathyroid adenomas among PHPT patients and to explore their correlations with biochemical parameters. Methods: Parathyroid adenoma samples were obtained from 20 PHPT patients who underwent parathyroidectomy. RNA was isolated, and gene expression levels were quantified using one-step reverse transcription quantitative PCR (RT-qPCR). Fold change values were calculated utilizing gene-specific patient average ΔCt values as references. Biochemical data, including serum calcium, phosphorus, PTH, and vitamin D (25-OH), as well as gender, age, and adenoma volumes, were statistically analyzed for correlation with gene expression patterns. Results: Gene expression analysis revealed significantly lower CaSR expression in small adenomas (<0.2 cm³) compared to medium and large adenomas, suggesting a possible association between tumor size and early molecular deregulation. Notably, CaSR expression exhibited a positive correlation with the expression levels of both VDR and FGFR1, suggesting the presence of a coordinated regulatory network encompassing calcium and vitamin D pathways. A multiple regression model revealed that serum vitamin D and PTH gene expression serve as positive predictors of CaSR expression, whereas serum PTH levels were negatively associated. A paradoxical positive correlation was observed between serum calcium levels and PTH gene expression, which may reflect impaired feedback control due to CaSR downregulation. Conclusion: These findings may provide new insights into the pathophysiology of PHPT, highlighting the importance of molecular profiling in understanding disease progression. The established expression patterns and their biochemical correlations may strengthen future efforts toward population-specific diagnosis and targeted therapeutic approaches, particularly in regions with high vitamin D deficiency and distinct disease severity profiles.

Keywords

• Primary hyperparathyroidism (PHPT)
• calcium-sensing receptor (CaSR)
• PTH
• vitamin D receptor (VDR)
• fibroblast growth factor receptor 1 (FGFR1)
• α-Klotho

Supporting Institution

This work was supported by Istanbul Okan University Scientific Research Projects Coordination under the Grant Number OBAP2024010002.

Project Number

OBAP2024010002

Ethical Statement

Ethical approval was obtained from the University of Health Sciences (SBU) Istanbul Training and Research Hospital, Clinical Research Ethics Committee (07.03.2025/52).

Thanks

The author gratefully acknowledges Prof. Dr. Erhan Ayşan for his invaluable support.

Türk primer hiperparatiroidizm hastalarında reseptör gen ekspresyonları ve klinik ve biyokimyasal parametrelerle ilişkisi

Abstract

Amaç: Primer hiperparatiroidizm (PHPT), aşırı paratiroid hormonu (PTH) salgılanmasıyla tanınır ve hiperkalsemiye ve sistemik komplikasyonlara yol açar. Bu çalışma, Türk PHPT hastalarında paratiroid adenomlarından PTH, kalsiyum algılayıcı reseptör (CaSR), vitamin D reseptörü (VDR), fibroblast büyüme faktörü reseptörü 1 (FGFR1) ve α-Klotho genlerinin ekspresyon profillerini araştırmayı ve bunların klinik ve biyokimyasal parametrelerle ilişkilerini incelemeyi amaçlamıştır. Yöntemler: Paratiroid adenom örnekleri, paratiroidektomi geçiren 20 PHPT hastasından elde edildi. RNA izole edildi ve gen ekspresyon düzeyleri tek adımlı ters transkripsiyon kantitatif PCR (RT-qPCR) kullanılarak ölçüldü. Kat değişim değerleri, gen spesifik hasta ortalama ΔCt değerleri referans olarak kullanılarak hesaplandı. Serum kalsiyum, fosfor, PTH ve vitamin D (25-OH) gibi biyokimyasal veriler ile cinsiyet, yaş ve adenom hacimleri, gen ekspresyon paternleri ile korelasyon açısından istatistiksel olarak analiz edildi. Sonuçlar: Gen ekspresyon analizi, küçük adenomlarda (<0,2 cm³) orta ve büyük adenomlara kıyasla CaSR ekspresyonunun önemli ölçüde daha düşük olduğunu ortaya koydu, bu da tümör boyutu ile erken moleküler düzensizlik arasında olası bir ilişki olduğunu düşündürdü. Özellikle, CaSR ekspresyonu hem VDR hem de FGFR1 ekspresyon düzeyleri ile pozitif korelasyon gösterdi, bu da kalsiyum ve vitamin D yolaklarını kapsayan koordineli bir düzenleyici ağın varlığını düşündürmektedir. Çoklu regresyon modeli, serum vitamin D ve PTH gen ekspresyonunun CaSR ekspresyonunun pozitif belirleyicileri olduğunu, serum PTH düzeylerinin ise negatif ilişkili olduğunu ortaya koydu. Serum kalsiyum düzeyleri ile PTH gen ekspresyonu arasında paradoksal bir pozitif korelasyon gözlemlenmiştir, bu da CaSR'nin aşağı regülasyonu nedeniyle bozulmuş geri besleme kontrolünü yansıtıyor olabilir. Sonuç: Bu bulgular, PHPT'nin patofizyolojisine yeni bir bakış açısı getirerek, hastalığın ilerlemesini anlamada moleküler profillemenin önemini vurgulamaktadır. Belirlenen ekspresyon paternleri ve bunların biyokimyasal korelasyonları, özellikle vitamin D eksikliğinin yüksek olduğu ve hastalık şiddetinin belirgin olduğu bölgelerde, popülasyona özgü tanı ve hedefe yönelik terapötik yaklaşımlara yönelik gelecekteki çabaları güçlendirebilir.

Keywords

• Kalsiyum algılayıcı reseptör (CaSR)
• PTH
• D vitamini reseptörü (VDR)
• Fibroblast büyüme faktörü reseptörü 1 (FGFR1)
• α-Klotho
• Primer hiperparatiroidizm (PHPT)

Project Number

OBAP2024010002

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