National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100037, China.
The First Affiliated Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan City), Huainan, 232000, Anhui, China.
J Hum Genet. 2023 Jun;68(6):393-398. doi: 10.1038/s10038-022-01118-w. Epub 2023 Feb 16.
Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β = 0.041, p = 0.01) and lower levels of serum creatinine (β = -0.068, p = 0.001) and serum uric acid (β = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.
肾功能变化和慢性肾脏病(CKD)进展与心血管疾病(CVD)风险相关,并受遗传因素影响。然而,在接受降压药物治疗的患者中,遗传变异与肾功能之间的关系仍不确定。本研究旨在探讨 30 个位于 22 个基因中的变异与 1911 例中国社区纵向队列高血压患者肾小球滤过率(eGFR)风险的关系(包括基线时 1220 例 CKD 患者和 691 例非 CKD 患者)。通过在调整年龄、性别、传统心血管危险因素和使用降压药物后,以及在多重比较校正后,使用多变量线性回归分析,携带金属磷酸酯酶结构域包含 2 号(MPPED2)基因 rs10767873T 等位基因的患者与更高水平的 eGFR(β=0.041,p=0.01)和更低的血清肌酐(β=-0.068,p=0.001)和血清尿酸(β=-0.047,p=0.02)相关。但是,无论使用何种类型的降压药物,rs10767873 变异均与 CKD 风险无关。在中位 2.25 年的随访期间,记录了 152 例 CVD 事件。有趣的是,与携带野生型 rs10767873CC 基因型的患者相比,携带 rs10767873TT 基因型的患者发生 CVD 事件的风险更高(危险比,1.74,95%置信区间,1.11 至 2.73;p=0.02)。总之,我们的研究结果表明,中国高血压患者 MPPED2 基因的 rs10767873 变异与肾功能和 CVD 风险相关。