Marozik Pavel M, Tamulaitiene Marija, Rudenka Ema, Alekna Vidmantas, Mosse Irma, Rudenka Alena, Samokhovec Volha, Kobets Katsiaryna
Laboratory of Human Genetics, Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, Minsk, Belarus.
Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Front Endocrinol (Lausanne). 2018 Jun 5;9:305. doi: 10.3389/fendo.2018.00305. eCollection 2018.
Vitamin D receptor (VDR) is one of the main mediators of vitamin D biological activity. VDR dysfunction might substantially contribute to development of postmenopausal osteoporosis (PMO). Numerous studies have revealed the effects of several gene variants on osteoporosis risk, although significant variation in different ethnicities have been suggested. The main purpose of this work was to assess the frequency of distribution of genetic variants with established effect and evaluate their haplotype association with the risk of PMO in a cohort of Belarusian and Lithuanian women. Case group included women with PMO ( = 149), the control group comprised women with normal bone mineral density (BMD) and without previous fragility fractures ( = 172). Both groups were matched for age, height, sex, and BMI-no statistically significant differences observed. gene polymorphic variants (ApaI rs7975232, BsmI rs1544410, TaqI rs731236, and Cdx2 rs11568820) were determined using polymerase chain reaction and restriction fragment length polymorphism. The lumbar spine (L1-L4) and femoral neck BMD was measured using dual-energy X-ray absorptiometry. Association between each variant and PMO risk was assessed using multiple logistic regression. The genotyping revealed statistically significant difference in the rs7975232 genotype frequencies between the patients and the controls (homozygous C/C genotype was overrepresented in patients, = 0.008). Patients with osteoporosis were also three times more likely to carry the rs1544410 G/G genotype, when compared to controls. We found that rs7975232, rs1544410, and rs731236 variants were in a strong direct linkage disequilibrium ( < 0.0001), suggesting that risk alleles of these markers are preferably inherited jointly. For the bearers of C-G-C haplotype (consisting of rs7975232, rs1544410, and rs731236 unfavorable alleles), the risk of PMO was significantly higher (OR = 4.7, 95% CI 2.8-8.1, < 0.0001) compared to controls. This haplotype was significantly over-represented in PMO group compared to all other haplotypes. Our findings highlight the importance of identified haplotypes of gene variants. Complex screening of these genetic markers can be used to implement personalized clinical approach for prevention, treatment, and rehabilitation programs.
维生素D受体（VDR）是维生素D生物活性的主要介质之一。VDR功能障碍可能在很大程度上导致绝经后骨质疏松症（PMO）的发生。众多研究揭示了几种基因变异对骨质疏松症风险的影响，不过也有人提出不同种族之间存在显著差异。这项研究的主要目的是评估具有既定效应的基因变异的分布频率，并在一组白俄罗斯和立陶宛女性中评估它们的单倍型与PMO风险的关联。病例组包括患有PMO的女性（n = 149），对照组由骨密度正常且既往无脆性骨折的女性组成（n = 172）。两组在年龄、身高、性别和BMI方面进行了匹配，未观察到统计学上的显著差异。使用聚合酶链反应和限制性片段长度多态性方法确定了4个基因多态性变异（ApaI rs7975232、BsmI rs1544410、TaqI rs731236和Cdx2 rs11568820）。使用双能X线吸收法测量腰椎（L1 - L4）和股骨颈的骨密度。使用多元逻辑回归评估每个变异与PMO风险之间的关联。基因分型显示患者和对照组之间rs7975232基因型频率存在统计学上的显著差异（纯合子C/C基因型在患者中过度表达，P = 0.008）。与对照组相比，患有骨质疏松症的患者携带rs1544410 G/G基因型的可能性也高出三倍。我们发现rs7975232、rs1544410和rs731236变异处于强直接连锁不平衡状态（P < 0.0001），这表明这些标记的风险等位基因更倾向于共同遗传。对于C - G - C单倍型（由rs7975232、rs1544410和rs731236的不利等位基因组成）的携带者，与对照组相比，PMO风险显著更高（OR = 4.7，95% CI 2.8 - 8.1，P < 0.0001）。与所有其他单倍型相比，该单倍型在PMO组中显著过度表达。我们的研究结果突出了所确定的基因变异单倍型的重要性。对这些遗传标记进行综合筛查可用于实施针对预防、治疗和康复计划的个性化临床方法。
