engleski

South African amaXhosa patients with atopic dermatitis have decreased stratum corneum natural moisturising factor but no loss- of-function mutations in filaggrin

The SC profiles of filaggrin breakdown products are highly informative in this African population as they provide a second look, in addition to direct sequencing, for FLG mutations. In our study we demonstrate that the diminution of filaggrin breakdown products is consistent with what we have seen in European AD patients who are wild type for FLG mutations. The magnitude of this reduction is much less than that seen in ADFLG, even in African patients with clinical findings consistent with IV, who could be expected to have FLG mutations. In Europeans with a single FLG LOF mutation, expression of these products is reduced by approximately 50%. We here provide strong and complementary evidence for an absence of FLG mutations in this African population through two different analytical methodologies. Given that FLG mutations are well established as the strongest and most important risk factor for AD in European, Japanese and Chinese populations, this work clearly implies significant genetic heterogeneity between AD in the African population and AD in these populations. The genetics of AD is not well studied in African populations ; in addition to the Ethiopian study referenced above, two studies in African American populations have found low frequencies of European-derived FLG mutations, presumably due to European population admixture. While it is tempting to speculate, based on this work, that there could be a major (non-FLG) African-specific gene for IV and/or AD, African populations will require specific studies and dedicated collections to disclose African population-specific major genetic risks for AD. In conclusion, FLG LOF mutations are not a significant contributor to AD in the amaXhosa population. When combined with previous findings in the Ethiopian population, the contribution of these mutations to AD in Africans seems to be at great variance with their major role in European and Asian populations. Further work is required in African populations to better understand the genetic basis of AD in these populations.

filaggrin ; FLG ; amaXhosa ; natural moisturizing factor ; atopic dermatitis ; eczema ; ichthyosis vulgaris ;

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