细胞黏着基因多态性与肾结石病风险的相关性研究  

Association between cell adhesion gene polymorphisms and the risk of nephrolithiasis

作　　者：郭梦茜 彭佳琦 于志豪 滕恩达 李可心 毕一凡 柳青 高兵[1] Guo Mengxi;Peng Jiaqi;Yu Zhihao;Teng Enda;Li Kexin;Bi Yifan;Liu Qing;Gao Bing(Department of Cell Biology and Genetics,Shenyang Medical College,Shenyang 110034,China;Department of Urology,Shenyang Red Cross Hospital,Shenyang 110034,China)

机构地区：[1]沈阳医学院细胞生物与遗传学教研室,沈阳110034 [2]沈阳市红十字医院泌尿外科,沈阳110034

出　　处：《国际遗传学杂志》2023年第1期14-23,共10页International Journal of Genetics

基　　金：国家自然科学基金(82070722);辽宁省创新能力提升联合基金(2022-NLTS-14-07);沈阳市科技创新平台建设计划市级重点实验室(18-007-0-02)。

摘　　要：目的探讨细胞黏着相关基因单核苷酸多态性(single nucleotide polymorphism,SNP)与肾结石风险的相关性。方法选择150例肾结石患者和150例健康人,采用高分辨熔解曲线(high resolution melting,HRM)方法对外显子组测序研究获得的细胞黏着相关候选基因(DGCR2 rs2072123、LAMB4 rs2528693、CDH2 rs17445840、ABL2 rs55655202、CX3CR1 rs3732379、ITGAE rs2976230和FLOT2 rs3736238)进行基因分型,分子相互作用分析多态性变异对蛋白结构的影响以及对基因功能注释。结果LAMB4 rs2528693风险等位基因G携带者增加罹患肾结石风险2.471倍(P=0.009,95%CI:1.231~4.957),增加男性罹患肾结石风险2.396倍(P=0.031,95%CI:1.061~5.411),尤其在中年年龄段增加罹患肾结石风险3.156倍(P=0.010,95%CI:1.160~8.586)。分子相互作用分析发现LAMB4 rs2528693变异导致分子间相互作用改变,可能影响蛋白结构的稳定性。基因相互作用分析发现风险基因LAMB4可能与细胞基质黏附有关。结论LAMB4 rs2528693 G等位基因显著增加肾结石风险,且与男性肾结石发病风险显著关联,为阐明细胞黏着基因在肾结石形成中的作用提供了依据。Objective To investigate the association between single nucleotide polymorphism(SNP)of cell adhesion related genes and the risk of nephrolithiasis.Methods 150 patients with kidney stones and 150 healthy people were selected and the cell adhesion-related candidate genes(DGCR2 rs2072123,LAMB4 rs2528693,CDH2 rs17445840,ABL2 rs55655202,CX3CR1 rs3732379,ITGAE rs2976230,FLOT2 rs3736238)were selected and obtained by high resolution melting(HRM)method for genotyping.Molecular interaction analysis of the effect of polymorphisms on protein structure and annotation of gene function.Results LAMB4 rs2528693 risk allele G carriers increased the risk of kidney stones by 2.471 times(P=0.009,95%CI:1.231~4.957),and the risk of kidney stones in men by 2.396 times(P=0.031,95%CI:1.061~5.411),especially in middle-aged age groups increased the risk of kidney stones 3.156-fold(P=0.010,95%CI:1.16~8.586).Molecular interaction analysis found that the variation of LAMB4 rs2528693 leads to changes in intermolecular interactions,which may affect the stability of protein structure.Gene interaction analysis found that the risk gene LAMB4 may be associated with cell matrix adhesion.Conclusion The LAMB4 rs2528693 G allele significantly increases the risk of kidney stones and is significantly associated with the risk of kidney stones in men,which provides a basis for elucidating the role of cellular adhesion genes in kidney stone formation.

关 键 词：肾结石 黏着 单核苷酸多态性 

分 类 号：R692.4[医药卫生—泌尿科学]