Lin Haisong, Zhu Xiujuan, Long Jun, Chen Yang, Xie Yuanliang, Liao Ming, Chen Jianxin, Tian Jiarong, Huang Shengzhu, Tang Ruiqiang, Xian Xiaoying, Wei Suchun, Wang Qiuyan, Mo Zengnan
Center for Genomic and Personalized Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Center for Genomic and Personalized Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China; Department of Urology, Guangxi Medical University Kaiyuan Langdong Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
Gene. 2018 May 5;653:51-56. doi: 10.1016/j.gene.2018.02.020. Epub 2018 Feb 8.
Recent studies have shown that genetic factors are involved in the development of kidney stone disease (KSD). A case-control association analysis was performed to investigate the association between homeodomain-interacting protein kinase 2 (HIPK2; OMIM *606868) polymorphisms and KSD.
A total of 890 KSD patients and 920 healthy subjects were analyzed. Polymorphisms were genotyped using SNPscanTM high-throughput SNP classification technology. The genotypic and allelic frequencies in KSD patients and healthy individuals were analyzed using a Chi-square test.
The genotype and allele distributions of the three polymorphisms (rs2058265, rs6464214, and rs7456421 in HIPK2) displayed strong associations with KSD in males (rs2058265: odds ratio [OR] 2.480,95%confidence interval [CI] 1.205-5.106, p = 0.014; rs6464214: OR 2.466, 95%CI 1.198-5.078, p = 0.014; rs7456421: OR 2.846, 95%CI 1.362-5.947, p = 0.005; perallele: r2058265T, OR 1.357, 95%CI 1.073-1.715, p = 0.011; rs6464214G, OR 1.340, 95%CI 1.060-1.693, p = 0.014; rs7456421C, OR 1.356, 95%CI 1.073-1.713, p = 0.011). Patients carrying the T allele of rs2058265, the G allele of rs6464214, or the C allele of rs7456421 showed higher systolic blood pressure, creatinine, and uric acid levels compared with wild-genotype individuals after adjusting for age, gender, and body mass index (p < 0.005).
The association of HIPK2 gene polymorphisms with KSD was only observed in males but not in females. HIPK2 gene polymorphisms were also involved in the changes of KSD-related metabolic traits.
近期研究表明，遗传因素参与了肾结石疾病（KSD）的发病过程。进行了一项病例对照关联分析，以研究同源结构域相互作用蛋白激酶2（HIPK2；OMIM *606868）基因多态性与KSD之间的关联。
共分析了890例KSD患者和920名健康受试者。使用SNPscanTM高通量SNP分型技术对基因多态性进行基因分型。采用卡方检验分析KSD患者和健康个体的基因型和等位基因频率。
三个多态性位点（HIPK2基因中的rs2058265、rs6464214和rs7456421）的基因型和等位基因分布在男性中与KSD显示出强关联（rs2058265：比值比[OR] 2.480，95%置信区间[CI] 1.205 - 5.106，p = 0.014；rs6464214：OR 2.466，95%CI 1.198 - 5.078，p = 0.014；rs7456421：OR 2.846，95%CI 1.362 - 5.947，p = 0.005；每个等位基因：rs2058265T，OR 1.357，95%CI 1.073 - 1.715，p = 0.011；rs6464214G，OR 1.340，95%CI 1.060 - 1.693，p = 0.014；rs7456421C，OR 1.356，95%CI 1.073 - 1.713，p = 0.011）。在调整年龄、性别和体重指数后，携带rs2058265的T等位基因、rs6464214的G等位基因或rs7456421的C等位基因的患者与野生基因型个体相比，收缩压、肌酐和尿酸水平更高（p < 0.005）。
仅在男性中观察到HIPK2基因多态性与KSD的关联，而在女性中未观察到。HIPK2基因多态性也参与了KSD相关代谢特征的变化。
