Background: Psoriasis is a chronic, immune-mediated skin disease affecting millions, marked by abnormal keratinocyte proliferation. Genetic factors, including the CARD14 gene, epigenetic mechanisms, alongside environmental triggers, drive immune hyperactivation and epidermal barrier dysfunction, influencing disease susceptibility and severity.

Objectives: To assess the role of CARD14 gene(rs34367357) polymorphism in Egyptian psoriatic patients.

Patients and methods: This cross-sectional study at Qena University Hospital included 40 adults with mild psoriasis vulgaris and 40 age and sex matched healthy controls, excluding individuals with other autoimmune disorders, pregnancy, or genetic immune conditions. Clinical assessment recorded demographics, disease history, BMI, and psoriasis severity using the PASI score (<10 defined as mild). Blood samples were collected for DNA extraction, and CARD14 rs34367357 polymorphism was genotyped using a TaqMan assay with real-time PCR.

Results: In mild psoriasis patients, demographics and lifestyle factors were similar to controls, but family history was significantly associated with disease (30% vs 0%, p<0.001). Mean PASI score was 3.53±0.78, with disease duration 2.34±1.39 years. Lesions primarily affected upper extremities (91.7%) and lower extremities (68.3%). The CARD14 rs34367357 G allele and AG/GG genotypes were significantly more frequent in cases than controls(p<0.001), and GG carriers had higher PASI scores(p<0.001). BMI positively correlated with PASI score(p=0.035), and family history also predicted higher severity(p=0.015), while other parameters and genotype showed no significant effect on disease course.

Conclusion: CARD14 rs34367357 G allele and GG genotype are key genetic risk factors for Egyptian psoriasis, associated with greater disease severity. Family history and higher BMI further exacerbate severity, emphasizing the combined influence of genetic and systemic factors.