Functional relevance for associations between osteoporosis and genetic variants

Abstract

Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (P<10−6), and 8 SNPs exert cis-regulation effects on 11 eQTL target genes. Among the 8 SNPs, 2 SNPs (RPL31 rs2278729 and LRP5 rs3736228) were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5) that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228) and 3 genes (RPL31, CPT1A and MTL5) with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis.

The low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism: candidate for susceptibility to type 1 diabetes mellitus

“…On the other hand, the LRP5 4037C>T is recognized as one of the key polymorphism in associated with increase the risk of bone fracture and osteoporosis, as well as in the cardiovascular diseases (12,(17)(18)(19)(20). In addition, it has been reported that the LRP5 4037C>T is associated with susceptibility to type 2 diabetes mellitus and osteoporosis in postmenopausal women.…”

The Mechanism of Mitochondrial Fatty Acid Oxidation’s Involvement in Osteoporosis in Aggravating Cartilage Degeneration of Rabbit Knee Osteoarthritis

“…Mitochondrial fatty acid β-oxidation is the major pathway for the catabolism of fatty acids, and it plays an essential role in maintaining whole body energy homeostasis. Studies have found that the CPT1A gene is associated with osteoporosis [7]. Therefore, we hypothesized that fatty acid oxidation is involved in the pathogenesis of OPOA.…”

The Brown Algae Ishige sinicola Extract Ameliorates Ovariectomy-Induced Bone Loss in Rats and Suppresses Osteoclastogenesis through Downregulation of NFATc1/c-Fos

“…However, the pathogenesis of postmenopausal osteoporosis has not been completely elucidated. In addition, there are certain limitations to treating osteoporosis through drugs, and they may have adverse effects, such as endometrial cancer, breast carcinoma, and cardiovascular disease [4][5][6]. Therefore, it is essential to develop natural or synthetic substances with few negative side effects, replacing or minimizing the need for current drugs used.…”