Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1

Abstract

Purpose: Osteopathy/osteoporosis in Gaucher disease type 1 (GD1) shows variable responses to enzyme replacement therapy (ERT); the pathogenesis is incompletely understood. We aimed to investigate the effects of several gene variants on bone mineral density (BMD) and serum markers of bone metabolism in GD1. Patients and methods: Fifty adult Caucasian patients with GD1/117 controls were genotyped for gene variants in the osteoprotegerin (TNFRSF11B; OPG), estrogen receptor alpha, calcitonin receptor (CALCR), and vitamin D receptor (VDR) genes. In patients and 50 matched healthy controls, we assessed clinical data, serum markers of bone metabolism, and subclinical inflammation. BMD was measured for the first time before/during ERT (median 6.7 years). Results: Forty-two percent of patients were splenectomized. ERT led to variable improvements in BMD. Distribution of gene variants was comparable between patients/controls. The AA genotype (c.1024+283G.A gene variant; VDR gene) was associated with lower Z scores before ERT vs GA (P=0.033), was encountered in 82.3% of patients with osteoporosis and was more frequent in patients with pathological fractures. Z score increases during ERT were higher in patients with the CC genotype (c.9C.G variant, TNFRSF11B; OPG gene; P=0.003) compared with GC (P=0.003). The CC genotype (c.1340T.C variant, CALCR gene) was associated with higher Z scores before ERT than the TT genotype (P=0.041) and was absent in osteoporosis. Osteocalcin and OPG were lower in patients vs controls; beta crosslaps, interleukin-6, and ferritin were higher. Conclusions: We suggest for the first time a protective role against osteoporosis in GD1 patients for the CC genotype of the c.9C.G gene variant in the TNFRSFB11 (OPG) gene and for the CC genotype of the c.1340T.C gene variant (CALCR gene), while the AA genotype of the c.1024+283G.A gene variant in the VDR gene appears as a risk factor for lower BMDs. Serum markers suggest decreased osteosynthesis, reduced inhibition of osteoclast activation, increased bone resorption, and subclinical inflammation during ERT.

Genes Polymorphism in Children with Diseases of the Nervous System Living in the Conditions of the Far North of Russia

“…The CALCR gene encodes calcitonin receptor membrane proteins on osteoclasts, kidney and liver cells. The presence of the T allele in the C1377T polymorphism can lead to a decrease in bone density, a decrease in the activation of the calcium receptor, which, under conditions of a deficit of insolation, leads to an increased risk of imbalance in the immune regulation of the cell life cycle, its atopic rearrangement and asthenization [14,18].…”

Association between Estrogen, Vitamin D and Microrna17 Gene Polymorphisms and Periapical Lesions

“…The genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and VDR (rs739837 and rs2228570) genes were selected based on their function in bone biology (28)(29)(30) and in their minor allele frequencies, that should be higher than 10%.…”