Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/92967
Title: WNT16 variants influence site-specific bone mass determination and fracture risk in Maltese postmenopausal women
Authors: Formosa, Melissa Marie
Mallia, Sarah Ann
Portelli, Warren
Xuereb-Anastasi, Angela
Keywords: Fractures -- Risk factors
Bone density
Genotype
Menopause -- Complications
Issue Date: 2021
Publisher: Elsevier
Citation: Formosa, M., Mallia, S., Portelli, W., & Xuereb-Anastasi, A. (2021). WNT16 variants influence site-specific bone mass determination and fracture risk in Maltese postmenopausal women. Bone Reports, 14, 100934.
Abstract: BACKGROUND/INTRODUCTION: Epidemiological studies and translational models have highlighted the importance of WNT16 as a key regulator of bone mineral density (BMD).
PURPOSE: The study aimed to investigate the effect of two WNT16 variants, a frameshift rs55710688 (insCCCA) in the Kozak sequence, and a single nucleotide variant rs3801387 (A>G) located in the last intron of WNT16, with BMD and fracture risk in the Maltese postmenopausal women.
METHODS: Genotyping was performed in 1,045 women from the Malta Osteoporotic Fracture Study using Competitive Allele Specific PCR (rs55710688) and TaqMan® fluorogenic 5’ nuclease allelic discrimination (rs3801387). Genotype-phenotype associations were analysed using the Mann-Whitney statistic whereas odds ratios (OR) with 95% confidence intervals [CI] were computed by logistic regression analysis adjusted for confounders.
RESULTS: Genotyping of the WNT16 rs55710688 and rs3801387 was successful in 1,038 (CCCA=24%) and 1,027 (G=27%) samples respectively. Women with the homozygous reference genotype for both WNT16 variants had a lower lumbar spine (LS) T-score relative to women with the homozygous alternative genotype (rs55710688 p=0.035; rs3801387 p=0.031). Risk ratios revealed that homozygosity for the reference alleles was associated with osteoporosis at the LS (rs55710688 adjusted-OR: 2.44 [1.16-5.13]; rs3801387: 2.40 [1.18-4.89]), and all-type of low-trauma fracture risk which was not attenuated by BMD (rs55710688: 2.17 [1.11-4.27]; rs3801387: 1.90 [1.05-3.55]). WNT16 rs55710688 reference genotype also exhibited a deleterious effect on femoral neck BMD (3.10 [1.05-9.15]). Finally, the haplotype with the reference alleles for WNT16 rs55710688 and rs3801387 was associated with LS BMD (p=0.007) and fracture risk (p=0.021).
CONCLUSION(S): Results indicate that the WNT16 rs55710688 and rs3801387 variants are possible genetic determinants of site-specific BMD and fracture risk in Malta, which is in line with other epidemiological studies. Our findings support the results of in vitro assays and in silico modelling demonstrating reduced translational efficiency in the presence of the reference alleles culminating in lower bone formation.
URI: https://www.um.edu.mt/library/oar/handle/123456789/92967
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