Possible association between actinic keratosis and the rs7208422 (c.917A→T, p.N306l) polymorphism of the EVER2 gene in patients without epidermodysplasia verruciformis.

BACKGROUND: Mutations of the EVER1 and EVER2 genes cause epidermodysplasia verruciformis (EV), a genodermatosis associated with squamous cell carcinoma (SCC). Recently, it has been found that the rs7208422 (c.917A→T, p.N306l) polymorphism in the EVER2 gene is related to an increased risk of SCC in patients with conditions other than EV. We hypothesized that this polymorphism might be also associated with actinic keratoses (AK). AIM: To determine whether the rs7208422 polymorphism of the EVER2 gene is associated with AK in non-EV patients. METHODS: We genotyped rs7208422 in 65 patients with AK and 274 controls, using reverse transcription PCR. RESULTS: We detected a trend towards an association between AK and the TT genotype of rs7208422; the frequency of this genotype was 38.5% in patients with AK and 26.3% in controls (OR  = â€Š1.75, P  < â€Š0.06 for recessive model of inheritance). We also found an association between rs7208422 TT and both the age at which AK appeared and the extent of the AK. This variant was more frequent in patients who had AK onset before the age of 70 years compared with those whose age of onset was above 70 years (OR = 3.14, P = 0.03 for the recessive model; OR = 2.05, P = 0.04 for allelic comparison) and more frequent in AK involving > 3 body areas (OR = 3.14, P = 0.03 for the recessive model; OR = 2.34, P = 0.01 for allelic comparison). These associations remained significant in a multivariate regression analysis, showing that both parameters were independently associated with the TT genotype (P = 0.031). CONCLUSIONS: This study indicates a potential role of the rs7208422 (c.917A→T, P.N306l) polymorphism of the EVER2 gene in AK.

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 + 5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense mutation in plant homeodomain (PHD) and three previously reported mutations (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376). Eleven patients had mutations on both chromosomes, whereas in three patients only a single alteration with proven or likely pathogenic effect was detected. The most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate was assessed in the background population. Analysis of 2008 samples showed eight heterozygotes, indicating the frequency of 0.40% (1:250) and the disease prevalence - 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000). Comparison with an epidemiological estimate (1:619,000, derived for women) suggested that in Poland, APECED is underdiagnosed. Among the patients, no genotype/phenotype correlations were found, but we noted that women had earlier onset of hypoparathyroidism (p < 0.02) and were younger at diagnosis (p < 0.05) than men.