Ding Qi, Cao Cheng, Shi Ying, Fan Zhijiang, Li Feng, Tu Wenjian, Jin Xiaohua, Zhu Hailiang, Fan Bo
Department of Urology, The First People's Hospital of Changshu, The Changshu Hospital Affiliated to Soochow University, Changshu, China.
Department of Gastroenterology, The First People's Hospital of Changshu, The Changshu Hospital Affiliated to Soochow University, Changshu, China.
Front Med (Lausanne). 2023 Jun 2;10:1175798. doi: 10.3389/fmed.2023.1175798. eCollection 2023.
The role of matrix metalloproteinase 9 (MMP-9) in the pathophysiology of chronic kidney disease (CKD), which is associated with a nearly two-fold greater risk for urinary calculi compared to people without CKD, has been demonstrated. The aim of the research is to evaluate the association between -1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk.
A hospital-based case-control study involving 302 kidney stone patients and 408 controls without kidney stone from southern China was conducted. Sanger sequencing was used to genotype the -1562C>T polymorphism. The serum MMP-9 was measured in 105 kidney stone patients and 77 controls by enzyme-linked immunosorbent assay.
Compared to the control group, the CT genotype was more frequent in nephrolithiasis patients (adjusted OR = 1.60, 95% CI = 1.09-2.37: the risk of developing nephrolithiasis in individuals with CT genotype compared to CC genotype). Moreover, there was also a higher frequency of CT/TT genotypes among patients with nephrolithiasis (adjusted OR = 1.49, 95% CI = 1.02-2.19: the risk of developing nephrolithiasis in individuals with CT/TT genotypes compared to CC genotype). The risk remained for the subgroups of patients aged >53, smokers with pack-years of smoking >20, non-drinkers, non-diabetic patients, patients with hypertension, recurrent episodes and calcium oxalate stones (OR = 2.26, 95% CI = 1.31-3.91; OR = 5.47, 95% CI = 1.10-27.30; OR = 1.76, 95% CI = 1.14-2.72; OR = 1.54, 95% CI = 1.03-2.30; OR = 1.97, 95% CI = 1.01-3.82; OR = 1.67, 95% CI = 1.06-2.62; OR = 1.54, 95% CI = 1.02-2.32, respectively). Biochemical parameters did not differ between genotypes. Compared to controls (18.57 ± 5.80 ng/mL), nephrolithiasis patients had significantly higher serum MMP-9 levels (30.17 ± 6.78 ng/mL, < 0.001). The serum MMP-9 levels of patients with CT/TT genotypes of -1562C>T were significantly higher than those with CC genotype (32.00 ± 6.33 vs. 29.13 ± 6.85 ng/mL, = 0.037).
The -1562C>T polymorphism in association with its soluble protein increased the risk of kidney stone, thus suggesting it could be used as a susceptibility biomarker for nephrolithiasis. Further functional studies and larger studies that include environmental exposure data are needed to confirm the findings.
基质金属蛋白酶9（MMP-9）在慢性肾脏病（CKD）病理生理学中的作用已得到证实，与无CKD的人相比，CKD患者患尿路结石的风险几乎高出两倍。本研究旨在评估-1562C>T多态性、MMP-9血清水平与肾结石风险之间的关联。
在中国南方进行了一项基于医院的病例对照研究，纳入302例肾结石患者和408例无肾结石的对照。采用桑格测序法对-1562C>T多态性进行基因分型。通过酶联免疫吸附测定法检测105例肾结石患者和77例对照的血清MMP-9水平。
与对照组相比，CT基因型在肾结石患者中更为常见（校正OR = 1.60，95%CI = 1.09-2.37：与CC基因型相比，CT基因型个体患肾结石的风险）。此外，肾结石患者中CT/TT基因型的频率也更高（校正OR = 1.49，95%CI = 1.02-2.19：与CC基因型相比，CT/TT基因型个体患肾结石的风险）。年龄>53岁的患者亚组、吸烟包年数>20的吸烟者、不饮酒者、非糖尿病患者、高血压患者、复发性发作患者和草酸钙结石患者的风险仍然存在（OR分别为2.26，95%CI = 1.31-3.91；OR = 5.47，95%CI = 1.10-27.30；OR = 1.76，95%CI = 1.14-2.72；OR = 1.54，95%CI = 1.03-2.30；OR = 1.97，95%CI = 1.01-3.82；OR = 1.67，95%CI = 1.06-2.62；OR = 1.54，95%CI = 1.02-2.32）。各基因型之间的生化参数无差异。与对照组（18.57±5.80 ng/mL）相比，肾结石患者的血清MMP-9水平显著更高（30.17±6.78 ng/mL，P<0.001）。-1562C>T的CT/TT基因型患者的血清MMP-9水平显著高于CC基因型患者（32.00±6.33 vs. 29.13±6.85 ng/mL，P = 0.037）。
-1562C>T多态性与其可溶性蛋白相关增加了肾结石风险，因此表明它可作为肾结石的易感性生物标志物。需要进一步的功能研究以及纳入环境暴露数据的更大规模研究来证实这些发现。
