FGF-2 Gene Polymorphism in Osteoporosis among Guangxi's Zhuang Chinese.

Xiaoyun Bin,Xiufeng Huang,Cory Xian,Qinghui Zhou,Chaowen Lin,Liping Wang

doi:10.3390/ijms18071358

Abstract

Osteoporosis is a complex multifactorial disorder of gradual bone loss and increased fracture risk. While previous studies have shown the importance of many genetic factors in determining peak bone mass and fragility fractures and in suggesting involvement of fibroblast growth factor-2 (FGF-2) in bone metabolism and bone mass, the relationship of FGF-2 genetic diversity with bone mass/osteoporosis has not yet been revealed. The current study investigated the potential relevance of FGF-2 gene polymorphism in osteoporosis among a Zhuang ethnic Chinese cohort of 623, including 237 normal bone mass controls, 227 osteopenia, and 159 osteoporosis of different ages. Bone density was examined by calcaneus ultrasound attenuation measurement, and single nucleotide polymorphisms (SNPs) and linkage disequilibrium analyses were performed on five SNP loci of FGF-2 gene. Significant differences were found in bone mass in males between the 45-year-old and ≥70-year-old groups (p < 0.01), and in females among 55, 60, 65 and 70-year-old groups (p < 0.05). Males had higher bone mass values than females in the same age (over 55-year-old) (p < 0.05). The proportions of individuals with normal bone mass decreased with age (65.2% to 40% in males, and 50% to 0% in females), whereas prevalence of osteoporosis increased with age (15.4% to 30% in men, and 7.7% to 82% in women). Out of five FGF-2 SNP loci, the TA genotype of rs308442 in the osteoporosis group (40.2%) was higher than in the control group (29.5%) (p < 0.05). The TA genotype was significantly correlated with the risk of osteoporosis (odds ratio OR = 1.653), 95% confidence interval (CI): 1.968–1.441). Strong linkage disequilibrium in FGF-2 gene was also detected between rs12644427 and rs3747676, between rs12644427 and rs3789138, and between rs3747676 and rs3789138 (D’ > 0.8, and r2 > 0.33). Thus, the rs308442 locus of FGF-2 gene is closely correlated to osteoporosis in this Zhuang ethnic Chinese cohort, and the TA may be the risk genotype of osteoporosis.

Highlights

Osteoporosis is a systemic skeletal disease characterized by a progressive reduction in bone mass and deterioration of the bone architecture and strength, resulting in an elevated risk of fracture [1]
It is believed that 50–85% of the variance in bone mineral density (BMD) and risks of osteoporosis is controlled by genetic factors which are mostly polygenic [2]
The current study has shown a clear relationship between FGF-2 gene polymorphism and bone mass, and by investigating single nucleotide polymorphism (SNP) and haplotype of FGF-2 gene and the risk of osteoporosis, FGF-2 gene was shown to be potentially useful genetic marker for predicting osteoporosis risk in senior and middle-aged Zhuang people

Summary

Introduction

Osteoporosis is a systemic skeletal disease characterized by a progressive reduction in bone mass and deterioration of the bone architecture and strength, resulting in an elevated risk of fracture [1]. The incidence of osteoporosis is influenced by heredity, environment, gender, age, nutrition, life style, physical exercise, drug use, disease, and various other factors. Among these factors, genetics accounts for 60–85% of the influence [2]. Bone morphogenetic protein (BMP) signaling pathway is critical for cartilage and bone formation and postnatal bone development and regulation of bone metabolism [9] Due to their critical roles in regulating bone mass, these factors are either currently and/or likely to be used as drug targets to intervene with the occurrence and development of osteoporosis. Further studies are required to identify other likely genetic factors for osteoporosis

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