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Background & objectives: Oxidative stress is known to have a causal role in hypertension. Klotho has emerged as a novel anti-aging molecule to inhibit oxidative stress at cellular level. This study aimed at evaluating the gene expression of klotho and antioxidative enzymes, manganese superoxide dismutase (Mn-SOD) and catalase, in peripheral blood mononuclear cells of essential hypertensive patients as compared to normotensive healthy controls. Methods: Ninety-nine newly diagnosed hypertensives and 103 age- and BMI-matched controls were recruited. The participants were non-diabetic and not on any medication. Soluble α-klotho levels were detected using enzyme-linked immunosorbent assay. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Results: Soluble α-klotho levels were significantly lower (27%, P=0.001) in patients as compared to controls. The trend remained same when compared against 44 out of 103 controls considered for gene expression analysis. Relative gene expression of klotho and catalase were 3-fold and 1.25-fold lower in patients as compared to controls, respectively. ΔCt value-based gene expression were also significantly lower for both genes (P=0.001). A decreasing but non-significant trend was observed for Mn-SOD gene expression. ΔCt value-based gene expression of catalase positively correlated with that of Mn-SOD in patient (rs=0.448) and control (rs=0.547) groups (P<0.001). In patients, the gene expression of Klotho positively correlated with that of catalase (rs=0.498, P=0.001), but not Mn-SOD (rs=0.155, P=0.126). Interpretation & conclusions: In the present study on newly diagnosed hypertensives, klotho and catalase gene expression were found to be significantly lower as compared to controls, indicating the role of oxidative stress in this patient group. In addition, a significant correlation between Klotho and catalase gene expression suggests a role for klotho in essential hypertension with respect to antioxidant defence.

α-Klotho, an anti-aging gene, has emerged as novel inhibitor of oxidative stress at cellular level. α-Klotho inhibits oxidative stress by inhibiting IGF-1/Insulin-FOXO (Forkhead box-O transcription factors) dependent deactivation of the antioxidative enzymes. The present study aimed at determining α-Klotho and Catalase gene expressions and Catalase activity in peripheral blood mononuclear cells (PBMCs) of essential hypertensive patients as compared to normotensive healthy controls in Indian population. Forty-eight hypertensives and 48 age, BMI-matched controls were recruited. Gene expression was evaluated by quantitative Real-Time PCR. Catalase enzyme activity in PBMCs and soluble α-Klotho levels in serum were detected using Enzyme-Linked Immunosorbent Assay. Gene expressions for α-Klotho and FOXO1 were significantly low (p<0.001 and p=0.002, respectively) in patients as compared to controls. Catalase expression was also low in hypertensive patients but did not reach statistical significance. However, there was strong positive correlation between ΔCt-based gene expression of α-Klotho and Catalase in patients (p<0.001) as well as controls (p=0.008). Positive correlation was also observed between gene expression of FOXO1 and that of α-Klotho (p=0.006) and Catalase (p=0.001) in hypertensives. Catalase activity in patients were significantly low (p<0.001) as compared to controls and positively correlated with soluble α-Klotho levels (rs=0.32, p=0.027), which were also 30.2% lower (p<0.001) in the patient group. Present study demonstrates low soluble levels and gene expression of anti-aging protein α-Klotho in hypertensive patients. α-Klotho may influence Catalase expression in essential hypertension through its effect on FOXO1 expression.

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