Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne

Abstract

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P combined ¼ 4.41 Â 10 À 9 and rs1060573, P combined ¼ 1.28 Â 10 À 8 ) and 1q24.2 (SELL, rs7531806, P combined ¼ 1.20 Â 10 À 8 ) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

“…Accordingly, mice overexpressing follistatin display reduced wound healing 18 , whereas overexpression of activin results in epidermal thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding 32 . Our study in European subjects did not detect associations at either of the two previously described acne risk loci 6 . We recognize that our study design, which used an unselected population control cohort in the discovery phase, may impact on the ability to detect true associations.…”

“…Genome-wide association studies (GWAS) have made a substantial contribution to the understanding of the genetic basis of several common cutaneous inflammatory disorders 4,5 . However, efforts to characterize the genetic basis of acne have thus far been limited 6,7 . In the Han Chinese population, two genome-wide significant acne susceptibility loci (1q24.2 and 11p11.2) have recently been identified through the study of 1,056 acne cases and 1,056 controls 6 .…”

“…However, efforts to characterize the genetic basis of acne have thus far been limited 6,7 . In the Han Chinese population, two genome-wide significant acne susceptibility loci (1q24.2 and 11p11.2) have recently been identified through the study of 1,056 acne cases and 1,056 controls 6 . The modest effect size (odds ratio (OR) of 1.22 and 1.23, respectively) of the reported loci together with the high heritability of acne suggest that additional well-powered GWAS, including studies in different populations, will provide an opportunity to discover further genetic determinants.…”

Pathogenesis of acne

“…Ennek oka egyelőre nem ismert. Kanadában végzett, európai eredetű populációt elemző tanulmányban a 8q24-es régióban található polimorfizmusok (rs4133274, rs13248513) és a serdülőkori acne között találtak összefüggést (38,39). Az azonosított SNP-k génszegény régióban, 72kb távolságban találhatóak a Myc proto-onkogéntől, és feltételezhetően az androgén receptor (AR) Myc által történő szabályozásán keresztül fejthetik ki hatásukat (40).…”

“…Az azonosított SNP-k génszegény régióban, 72kb távolságban találhatóak a Myc proto-onkogéntől, és feltételezhetően az androgén receptor (AR) Myc által történő szabályozásán keresztül fejthetik ki hatásukat (40). Kínai populációban végzett vizsgálatokban szintén az androgén metabolizmus folyamatában szerepet játszó gének polimorfizmusait azonosították (39). Ezzel szemben brit tanulmányban Navarini és munkatársai acnéval összefüggésben eddig kevésbé vizsgált útvonal, a transzformáló növekedési faktor béta (transforming growth factor beta -TGF-β) szerepét vetették fel (41).…”