Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.
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.
Heikkinen
Anna-Mari
AM
Department of Obstetrics and Gynecology, Kuopio University Hospital, FIN-70211 Kuopio, Finland.
Niskanen
Leo K
LK
Salmi
Jukka A
JA
Koulu
Markku
M
Pesonen
Ullamari
U
Uusitupa
Matti I J
MI
Komulainen
Marja H
MH
Tuppurainen
Marjo T
MT
Kröger
Heikki
H
Jurvelin
Jukka
J
Saarikoski
Seppo
S
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*
D009478:Neuropeptide Y; D011498:Protein Precursors; D021382:Protein Sorting Signals; C042084:preproneuropeptide Y; D011392:Proline; D007930:Leucine