Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625 021, India.
Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, USA.
Mol Biol Rep. 2023 Sep;50(9):7581-7588. doi: 10.1007/s11033-023-08676-y. Epub 2023 Jul 31.
Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. The variations of HP gene affect its enzyme activity, resulting in varied antioxidant, angiogenic and anti-inflammatory properties. HP 2-2 genotype showed 3.84 fold increased risk for the development of CKD in Taiwan population. With this background, the present work focused to conduct a prospective case-control study in South Indian population to evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) conditions.
Totally 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. The blood samples collected from the patients were used to determine biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results showed that HP 2-2 genotypes were significantly associated with ND and ESRD disease development compared to controls. Higher HP2-2 genotype frequency showed an increased hazard ratio for overall disease progression among ND patients (hazard ratio = 3.86; 95% CI 1.88 to 7.93; P = 0.0002). Survival analysis also showed that non-HP2-2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP2-2 genotype (ESRD patients hazard ratio = 4.05; P = 0.04).
The present study confirms that HP2-2 polymorphism is statistically associated with the risk of CKD incidence, progression, and mortality among South Indians. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.
触珠蛋白（HP）是一种血浆糖蛋白，可与游离血红蛋白结合，防止铁丢失和肾脏损伤。HP 基因的变异影响其酶活性，导致抗氧化、血管生成和抗炎特性的不同。台湾人群的研究显示 HP2-2 基因型使 CKD 的发生风险增加了 3.84 倍。基于这一背景，本研究在印度南部人群中进行了一项前瞻性病例对照研究，以评估 HP 变异是否与非透析（CKD 1-4 期）和终末期肾病（CKD 5 期）相关。
共纳入 392 名 CKD 患者（非透析，ND；n=170，终末期肾病，ESRD；n=222）和 202 名健康对照者。从患者采集血样以确定生化参数和 HP 基因分型。对基因频率和生化参数进行统计学分析以评估疾病相关性。结果显示，与对照组相比，HP2-2 基因型与 ND 和 ESRD 疾病的发生显著相关。在 ND 患者中，HP2-2 基因型的频率较高与总体疾病进展的风险增加相关（风险比=3.86；95%CI 1.88 至 7.93；P=0.0002）。生存分析还显示，非-HP2-2 患者的死亡率明显低于 HP2-2 基因型患者（ESRD 患者风险比=4.05；P=0.04）。
本研究证实 HP2-2 多态性与南印度人群 CKD 发生率、进展和死亡率的风险相关。我们的结论是，HP2-2 基因型可能是 CKD 患者全因死亡率和疾病进展的独立预测因子。
