title: Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.
abstract: Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, FIN-70211 Kuopio, Finland.
authors.forename: Anna-Mari
authors.initials: AM
authors.lastname: Heikkinen
authors.forename: Leo K
authors.initials: LK
authors.lastname: Niskanen
authors.forename: Jukka A
authors.initials: JA
authors.lastname: Salmi
authors.forename: Markku
authors.initials: M
authors.lastname: Koulu
authors.forename: Ullamari
authors.initials: U
authors.lastname: Pesonen
authors.forename: Matti I J
authors.initials: MI
authors.lastname: Uusitupa
authors.forename: Marja H
authors.initials: MH
authors.lastname: Komulainen
authors.forename: Marjo T
authors.initials: MT
authors.lastname: Tuppurainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Kröger
authors.forename: Jukka
authors.initials: J
authors.lastname: Jurvelin
authors.forename: Seppo
authors.initials: S
authors.lastname: Saarikoski
mesh_terms: D015519:Bone Density / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D005272:Femur Neck / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000235:genetics*; D011392:Proline / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics*
chemical_list: D009478:Neuropeptide Y; D011498:Protein Precursors; D021382:Protein Sorting Signals; C042084:preproneuropeptide Y; D011392:Proline; D007930:Leucine