title: Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.
abstract: BACKGROUND
  Osteoporosis, characterized by low bone mineral density (BMD) and high bone fracture risk, is prevalent in Thai menopausal women. Genetic factors are known to play a key role in BMD. Low density lipoprotein receptor-related protein 5 (LRP5), a co-receptor in the Wnt/beta-catenin pathway, is involved in many aspects of bone biology. As coding single nucleotide polymorphisms (cSNPs) of LRP5, including A1330V (rs3736228), and Asian-related Q89R (rs41494349) and N740N (rs2306862), are associated with lowered BMD, this study aimed to determine the relationship between these LRP5 polymorphisms and BMD in 277 Thai menopausal women.
  
  
  RESULTS
  Only rs3736228 deviated from the Hardy-Weinberg equilibrium of allele frequency (p = 0.022). The median, range and p value for the BMD related to each SNP parameter were compared (Mann-Whitney U test). Significant differences were observed between wild-type and risk alleles for both rs3736228 (total radial, p = 0.011; and radial 33, p = 0.001) and rs2306862 (radial 33: p = 0.015) SNPs, with no significant difference for rs41494349 SNP. Linkage disequilibrium was strong for both rs3736228 and rs2306862 SNPs. Haplotype analysis identified high CC frequency in both normal and osteopenia/osteoporosis groups, with a significant odds ratio for carrying the TT haplotype; however, this was non-significant after adjusting for age. Multivariate binary logistic regression analysis performed for rs3736228 showed that individuals with a body mass index <25 kg/m(2) had an increased risk of osteoporosis for each decade, but the polymorphism had no effect.
  
  
  CONCLUSIONS
  This study did not identify LRP5 polymorphisms as a risk factor for osteoporosis in Thai menopausal women. Further studies with larger sample sizes are needed to further clarify the role of LRP5 as a genetic determinant of osteoporosis.
authors: Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. anong.kit@mahidol.ac.th.
authors: Anong
authors: A
authors: Kitjaroentham
authors: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Hathairad
authors: H
authors: Hananantachai
authors: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Benjaluck
authors: B
authors: Phonrat
authors: Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Sangchai
authors: S
authors: Preutthipan
authors: Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Rungsunn
authors: R
authors: Tungtrongchitr
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013785:Thailand
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5
keywords: Coding single nucleotide polymorphisms; Low density lipoprotein receptor-related protein 5 (LRP5); Menopausal Thai women; Osteopenia; Osteoporosis