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This study was designed to identify a parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene polymorphism in a healthy Japanese population. All known 13 introns of this gene were amplified by PCR, except the 1st intron, which was amplified by the long-PCR method. No restriction fragment length polymorphisms (RFLPs) were detected by BsmI or XbaI in any of these introns. Twenty-one other restriction enzymes (Hind III, Bgl II, Sty I, Pvu II, Eco81 I, Van91 I, BstX I, Sse8387 I, EcoR I, BamH I, Mbo II, Tth111 I, PshA I, Eam1105 I, Not I, Srf I, Bgl I, Fok I, Sfi I, Apa I, Taq I) were tested on the 1st intron. Furthermore, digestion by Van911 (CCATGG) identified a single, two-allele polymorphism with a fragment of approximately 3.5 kb (V allele) or a fragment of 3.1 and 0.4 kb (v allele). The frequency of the Van91 I polymorphism in 106 healthy Japanese volunteers was 77.4% for type vv, 19.8% for type Vv and 2.8% for type VV. In addition, the urinary cAMP response to exogenous [1-34]PTH was studied in 17 healthy volunteers and found to be significantly greater in persons with type Vv than type vv (p&lt;0.05). In conclusion, the Van91 I polymorphism of the PTH/PTHrP receptor gene can be used to study the role of polymorphism in various disorders involving PTH or PTHrP.

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A Novel Van91 I Polymorphism in the 1st Intron of the Parathyroid Hormone(PTH)/PTH-Related Peptide(PTHrP) Receptor Gene and Its Effect on the Urinary cAMP Response to PTH.