Relationship between klotho and psoriasis: A cross-sectional analysis of NHANES 2009-2010 and Mendelian randomization...

Psoriasis commonly presents with systemic comorbidities as a chronic, immune-mediated condition. The antiaging protein klotho, recognized for its dual anti-inflammatory and antioxidant properties, may modulate psoriasis pathogenesis, although human data are currently scarce. This cross-sectional analysis enrolled 1407 participants, including 50 with psoriasis. Serum klotho was log10-transformed, and multivariable logistic regression was used to assess its association with psoriasis. Restricted cubic spline analysis was performed to evaluate potential nonlinearity. Kaplan-Meier curves were used as unadjusted descriptive survival analyses, and Cox proportional hazards models were fitted among participants with psoriasis. Causal relationships were further assessed using Mendelian randomization. Lower serum klotho levels were independently associated with a higher prevalence of psoriasis after full adjustment (odds ratio = 0.11, 95% confidence interval: 0.02-0.80, P = .029). Restricted cubic spline analysis suggested a borderline overall association (P for overall = .055) without significant evidence of nonlinearity (P for nonlinearity = .344). Among participants with psoriasis, low klotho defined using the optimal cutoff of 2.92 was associated with poorer survival in unadjusted Kaplan-Meier analysis (P = .031), and higher log10-transformed klotho was associated with a lower risk of all-cause mortality in the fully adjusted Cox model. Mendelian randomization found no evidence of a causal association between genetically predicted klotho and psoriasis but suggested a potential protective effect against arthritis. Reduced serum klotho levels are associated with psoriasis prevalence, metabolic comorbidities, and mortality among participants with psoriasis. Klotho may represent a candidate biomarker related to inflammatory and cardiometabolic risk in psoriasis; however, causal and prognostic implications require validation in prospective cohorts and mechanistic studies.