Multiple endocrine neoplasia type 1 polymorphism D418D is associated with sporadic primary hyperparathyroidism

Sporadic primary hyperparathyroidism (pHPT) occurs separately and in several hereditary disorders including multiple endocrine neoplasia type 1. Irradiation to the neck, female gender, and age are well-identified risk factors that predispose to pHPT. The multiple endocrine neoplasia type 1 gene is the most commonly deranged gene in parathyroid adenomas and contains several polymorphisms including D418D with a prevalence of roughly 50%.

We genotyped 162 pHPT patients and control participants to evaluate if the D418D polymorphism is related to development of pHPT. One hundred fourteen of the pHPT patients and control participants were recruited from a health screening and were subjected to measurement of bone mineral density (BMD) at the lumbar spine, femoral neck, and total body.

The prevalence of each genotype (ie, MM, Mm, and mm) was for all pHPT patients: 62%, 29%, and 9%; and for all control participants: 32%, 43%, and 25% (P <.0004). For the screening-detected pHPT patients and control participants, the genotype distribution for MM, Mm, and mm was 60%, 30%, and 10%; and 31%, 44%, and 25%, respectively (P =.009). In the screening-recruited control participants, but not in pHPT patients, the MM genotype was also associated with higher total body BMD (P =.01) and BMD at the femoral neck (P =.02), whereas it failed to be significant for BMD at the lumbar spine (P =.08).

We report that the MM genotype was overrepresented in pHPT patients compared with control participants, suggesting a novel marker for pHPT. Furthermore, the MM genotype was associated with higher BMD at the femoral neck and in the total body in the screening-recruited control participants.