Low-density lipoprotein receptor-related protein 5 and vitamin D receptor gene polymorphisms in relation to vitamin D levels in menopause.
BACKGROUND
The low-density lipoprotein receptor-related protein 5 (LRP5) gene has been recently identified as a novel candidate for osteoporosis. The c.4037C>T polymorphism in the LRP5 gene has been associated with bone mass variance in general population. In contrast, the IVS8+443G>A polymorphism in the vitamin D receptor gene (VDR) has not been investigated in relation to bone metabolism. The aim of the present study was to determine VDR IVS8+443G>A and LRP5 c.4037C>T polymorphisms in a cohort of 165 perimenopausal women and to associate the genotypes with biochemical and densitometric bone parameters in a subset of 112 postmenopausal women.


METHODS
Both polymorphisms were assessed by restriction analysis of the PCR product. Calcium, parathyroid hormone, vitamin D metabolites and bone mineral density (BMD, g/cm(2)) at the hip and in the spine (L(1)-L(4)) were examined.


RESULTS
The genotype frequencies of both IVS8+443G>A (UU 75.2%, Uu 23%, uu 1.8%) and c.4037C>T (CC 73.9% TC 23.6%, TT 2.4%) were comparable to other Caucasian female cohorts. Serum 25OH vitamin D levels, assessed in only 63 probands, were significantly associated with VDR genotypes (ANCOVA, p<or=0.0027). We did not find any associations between LRP5 genotypes and bone or hormonal characteristics.


CONCLUSIONS
VDR IVS8+443G>A polymorphism was significantly associated with circulating 25OH vitamin D in postmenopausal Caucasian women. The role of candidate gene polymorphisms in the vitamin D metabolic pathway requires further investigation.
Zajickova
Katerina
K
Institute of Endocrinology, Prague, Czech Republic. kzajickova@endo.cz
Hill
Martin
M
Vankova
Marketa
M
Zofkova
Ivana
I
D000368:Aged; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D005260:Female; D005838:Genotype; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism; D008593:Menopause / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011859:Radiography; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D013131:Spine / Q000000981:diagnostic imaging; D014807:Vitamin D / Q000097:blood* / Q000235:genetics
D026502:LDL-Receptor Related Proteins; D018167:Receptors, Calcitriol; D014807:Vitamin D