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

This study was designed to identify a parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene polymorphism in a healthy Japanese populatio n. 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, Pv u 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 Van91 I (CCANNNNNTGG) i dentified a single, two-allele polymorphism with a fragment of approximatel y 3.5 (upsilon allele) or a fragment of 3.1 and 0.4 kb (upsilon allele), Th e frequency of the Van91 I polymorphism in 106 healthy Japanese volunteers was 77.4% for type upsilon upsilon, 19.8% for type V upsilon and 2.8% for t ype VV. In addition, the urinary cAMP response to exogenous [1-34]PTH was s tudied in 17 healthy volunteers and found to be significantly greater in pe rsons with type V upsilon than type upsilon upsilon (p<0.05). In conclusion , the Van91 I polymorphism of the PTH/PTHrP receptor gene can be used to st udy the role of polymorphism in various disorders involving PTH or PTHrP.