Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy.
Endocrine. 2023 Dec;82(3):646-653. doi: 10.1007/s12020-023-03476-7. Epub 2023 Aug 31.
Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism.
Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis.
The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes.
Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies.
高钙甲状旁腺功能亢进症（PHPT）是一种常见的内分泌疾病，其特征已经得到很好的描述。相比之下，许多低钙甲状旁腺功能亢进症（NPHPT）的方面，如自然史、器官损伤和管理，仍存在争议。此外，NPHPT 的病理生理学和分子基础尚不清楚。我们研究了 PHPT 和 NPHPT 患者群体是否具有相同的基因遗传变异模式，这些基因已知与钙和/或骨代谢有关。
对在三级转诊中心评估的 27 名 NPHPT 和 31 名 PHPT 患者进行了 9 个单核苷酸多态性（SNP）的基因分型，通过实时 PCR（TaqMan 分析）进行。将两组数据与 54 名内部对照和 503 名 1000 基因组计划参与者进行比较。对单个基因座、两个基因座和多个基因座的等位基因/单倍型频率进行了比较。
在 OPG 和 ESR1 的 SNP 中，NPHPT 组差异显著。此外，NPHPT 队列在基因型和不常见的多基因座基因型的成对关联方面具有独特性。
我们的 NPHPT 患者组比其他样本具有更大的遗传多样性。特定的基因型可能有助于定义 NPHPT 患者的亚组，这些亚组需要进行专门的临床和随访研究。
