LCE3B – Psoriasis

LCE3B has been implicated in psoriasis through several independent genetic association studies. In a Tunisian cohort, a common deletion affecting both LCE3B and LCE3C was analyzed in 180 psoriatic patients and 208 controls, and a significantly higher deletion frequency was observed in patients with a positive family history (PMID:22926764). This evidence supports the role of LCE3B in familial forms of psoriasis.

The overall clinical validity of the association is rated as Moderate. This rating is based on replication of the association in diverse populations, including evidence from family‐based subanalyses as well as from case series and genome‑wide analyses (PMID:22926764; PMID:27564082; PMID:25481369).

Genetically, the evidence comprises association studies where the variant, represented here as c.1_50del (p.Met1TrpfsTer17), was identified in affected individuals with familial history. Although the exact variant details differ between studies, the recurrent deletion involving LCE3B in the context of psoriasis has been consistently observed, underscoring its contributory risk profile.

Despite psoriasis being a complex trait, the segregation pattern seen in the familial subset suggests a pattern that might approximate autosomal dominant inheritance in affected families. However, explicit segregation counts are limited (with additional affected relatives reported as 0 in the available data). The genetic evidence indicates a moderate contribution of LCE3B to disease risk through common deletion alleles.

Functional data specific to LCE3B are scarce in the supplied evidence. Although the deletion is presumed to affect skin barrier function—a critical factor in psoriasis pathogenesis—no direct functional assays, expression studies, or animal models were detailed. This gap results in a limited functional evidence score despite the genetic associations.

In summary, multiple association studies across distinct populations, particularly in familial psoriasis cases, support a moderate gene–disease association for LCE3B with psoriasis. Key take‑home sentence: The LCE3B deletion represents a promising genetic marker for familial psoriasis, offering potential utility in both diagnostic decision‑making and personalized treatment approaches.

References

• Archives of dermatological research • 2012 • Association analysis of LCE3C-LCE3B deletion in Tunisian psoriatic population PMID:22926764
• The British journal of dermatology • 2017 • Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis PMID:27564082
• Molecular immunology • 2015 • Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis PMID:25481369

Evidence Based Scoring (AI generated)