Department of Biotechnology, Lahore College for Women University, Lahore, Pakistan.
Department of Biotechnology, Kinnaird College for Women, Lahore, Pakistan.
Mol Biol Rep. 2023 Oct;50(10):8049-8059. doi: 10.1007/s11033-023-08681-1. Epub 2023 Aug 4.
Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder that leads to reduced cerebral cortex caused by a mutation in corticogenesis. The expression of the Vitamin D receptor (VDR) gene is involved in the proliferation and differentiation of neural stem cells, and VDR polymorphisms have been associated with various neurological disorders. However, their relationship with MCPH has not been explored. This study aimed to investigate the association of VDR polymorphisms with MCPH due to its role in Wnt signaling pathway and its In-silico analysis.
Blood samples of 64 MCPH patients and 52 controls were collected to genotype VDR SNPs (TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). In-silico tools were also used to assess the effects of exonic SNPs on mRNA and protein structure and pathogenicity of exonic and intronic SNPs.
The study found that serum 25-OH vitamin D3 levels were significantly different in MCPH patients and healthy controls (P = 0.000). The genetic analysis showed that VDR polymorphisms of FokI and BsmI were seven times more frequent in MCPH patients than in controls (P < 0.05) and the recessive model for TaqI and dominant model for BsmI polymorphisms were also associated with the pathogenesis of MCPH. In-silico analysis showed that the pathogenicity effects of rs2228570 and rs1544410 are neutral while rs731236 causes a silent mutation which has no effect on VDR protein.
VDR polymorphisms of FokI and BsmI are associated with the risk of MCPH. These findings suggest that VDR polymorphisms play a role in MCPH, which could provide important insights for understanding the molecular mechanisms of the disease.
常染色体隐性原发性小头畸形（MCPH）是一种罕见的遗传疾病，由于皮质发生过程中的突变导致大脑皮层减少。维生素 D 受体（VDR）基因的表达参与神经干细胞的增殖和分化，VDR 多态性与各种神经疾病有关。然而，它们与 MCPH 的关系尚未得到探索。本研究旨在探讨 VDR 多态性与 MCPH 的关系，因为它在 Wnt 信号通路中的作用及其在计算机中的分析。
采集 64 例 MCPH 患者和 52 例对照者的血样，对 VDR 单核苷酸多态性（TaqI(rs731236)、FokI(rs2228570)和 BsmI(rs1544410)进行基因分型。还使用计算机工具来评估外显子单核苷酸多态性对 mRNA 和蛋白质结构以及外显子和内含子单核苷酸多态性的致病性的影响。
研究发现，MCPH 患者和健康对照组的血清 25-羟维生素 D3 水平有显著差异（P=0.000）。遗传分析显示，FokI 和 BsmI 的 VDR 多态性在 MCPH 患者中比在对照组中频繁 7 倍（P<0.05），TaqI 的隐性模型和 BsmI 的显性模型也与 MCPH 的发病机制有关。计算机分析表明，rs2228570 和 rs1544410 的致病性效应是中性的，而 rs731236 导致无义突变，对 VDR 蛋白没有影响。
FokI 和 BsmI 的 VDR 多态性与 MCPH 的风险相关。这些发现表明，VDR 多态性在 MCPH 中起作用，这为理解疾病的分子机制提供了重要的见解。
