A small proline-rich protein (SPRR) gene variant contributes to atopic eczema and eczema-associated asthma susceptibility

INTRODUCTION: There is some evidence that genetic variants in the epidermal differentiation complex (EDC) genes on chromosome 1q21 may be involved in the pathogenesis of atopic eczema (AE) similar to the well-known filaggrin gene (FLG) mutations. AIM: To evaluate the association of SNP in the small proline-rich protein 2B (SPRR2B) gene with atopic eczema and other allergic phenotypes and to investigate its possible interaction with FLG mutations. MATERIAL AND METHODS: One hundred and eighty-eight children less than 2 years old were screened for the variant of allele rs6693927 in the SPRR2B gene and for 4 most prevalent FLG mutations. The variant of allele rs6693927 and all FLG mutations were genotyped by real-time polymerase chain reaction assays with subsequent melting curve analysis using SimpleProbe(®) probes. RESULTS: The allele rs6693927[A] was associated with a significantly increased risk of AE (OR = 3.02; 95% CI: 1.17–8.00; p = 0.011) and the effect was independent of FLG risk alleles. The largest effects were observed in patients with a combined asthma-plus-eczema phenotype (OR = 5.44; 95% CI: 1.17–25.16; p = 0.029). Finally, in eczema, we found interactions of rs6693927[A] with FLG mutations, the risk of eczema was the most increased in the subjects who combined both rs6693927[A] allele and FLG mutations. CONCLUSIONS: The SPRR2B risk variant may play an important role in the development of atopic eczema and the particular eczema-associated asthma phenotype in young children. The effect seems to be independent of, and supplementary to, the well-known FLG mutations and may be modulated by gene-gene interactions.