Acne Genetics

The genetic influence on pathogenesis of acne is well documented in twins [30] and genealogic studies. In some types of acne, such as acne conglobata, hereditary factors are more apparent, and a correlation has been suggested between neonatal acne and familial hyperandrogenism [4]. Nodulocystic IA is often observed in relatives of patients with extensive steatocystoma, adolescent and postadolescent acne [31]. Fifty percent of postadolescent acne patients have at least one first-degree relative with the condition [32].

Sebum excretion also correlates with acne susceptibility, and sebum excretion rates are similar in identical twins [33]. Several chromosomal abnormalities, including 46XYY genotype [34], 46XY+ (4p+; 14q-) [35], and partial trisomy 13 [36] have been reported to be associated with nodulocystic acne.

The relationship of acne and various genes has been investigated. An HLA antigen study was negative for acne conglobata [37], but HLA phenotypes were identical in siblings affected with familial acne fulminans [38]. Polymorphism in the human cytochrome P-450 1A1 (CYP1A1) seem to be associated with acne [39], and CYP1A1 is known to be involved in the metabolism of a wide range of compounds such as vitamin A. In acne patients, a higher frequency of CYP1A1 mutation was observed on regulatory sites, and this may impair the biological efficacy of natural retinoids due to their rapid metabolism to inactive compounds. This mutation may thus be involved in the pathogenesis of acne in some patients. CYP1A1 inducibility is determined by polymorphism in the genes of the aromatic hydrocarbon (Ah) receptor. This Ah receptor mediates the toxic effects of environmental pollutants such as dioxin and polyhalogen-ated biphenyls. Clinical correlations between the high inducibility of CYP1A1 and some carcinomas are observed; however, no correlation was found between polymorphism of the human Ah receptor and 2,3,7,8-tetra-chlorodibenzo-p-dioxin-induced chloracne in chemical workers accidentally exposed to this chemical [40].

An inadequate activity of steroid 21-hydroxylase, as well as CYP21 gene mutations, is the genetic basis for congenital or late-onset adrenal hyperplasia which may present with acne. Acne patients exhibit a high frequency of a CYP21 gene mutation, but a poor correlation exists between mutations and either elevated steroids or acne [41]. It has been suggested that factors other than mild impairment of CYP21 can contribute to the clinical phe-notype that includes acne.

Androgen receptor polymorphisms of CAG trinucleo-tide repeat length has clinical implications for human disease. This polymorphism exhibits a correlation with some androgenic skin diseases but not with acne [42].

MUC1 is a glycoprotein secreted from various epithelial glands including sebaceous glands. Studies of the respiratory and digestive systems suggest that MUC1 is involved in the defense system against bacteria by inhibiting their adhesion to epithelium. The MUC1 gene and the molecule produced exhibit extensive polymorphism attributable to a variable number of tandem repeats. A higher frequency of longer repeat length of tandem repeats has been observed in severe acne patients [43].

The melanocortin 5 receptor is known to regulate sebaceous gland function in mouse. Genetic diversity is observed in human melanocortin 5 receptor coding region. Association between variation at the locus and acne is not found [44].

In conclusion, the pathogenesis of acne is multifacto-rial and a greater number of genes than those cited above are probably related to the condition. Genes affecting ker-atinization and desquamation are suspected to be involved in the pathogenesis of acne and their correlation to acne is yet to be evaluated. Advances in immunogenetic research may shed new light on the understanding of the inflammatory reaction in acne. Genes expressed in the sebaceous glands which exhibit polymorphism are of special interest, regardless of their known function. Any gene polymorphisms found to be related to acne may provide additional insights into the pathogenesis of this condition. Further research is needed to investigate the combined effects of these and other genes.


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Dermatology 2003;206:29-36 DOI: 10.1159/000067820

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