SKINIPEDIA - Skin Encyclopedia: Acne in Women (Genetics)

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The Influence of Genetics and Environmental Factors in the Pathogenesis of Acne: A Twin Study of Acne in Women

by V Bataille*,†, H Snieder*, A J MacGregor*,‡, P Sasieni‡ and T D Spector*

  1. *Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London, U.K.
  2. †Georgia Prevention Institute, Medical College of Georgia, Augusta, GA, U.S.A.
  3. ‡Department of Mathematics, Statistics and Epidemiology, Cancer Research U.K., London, U.K.

Correspondence: Dr Veronique Bataille MD PhD FRCP, Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London SE1 7HT, U.K. Email: vbataille@twin-research.ac.uk

DISCUSSION

Hormonal factors (endogenous or exogenous) are thought to play an important part in acne in view of the onset of the disease around puberty, the relationship between acne and hyperandrogenism and the therapeutic effect of anti-androgenic agents. Furthermore, an association between PCO and acne has also long been established (Sheehan et al, 1988;Rosenfield, 1986;Betti et al, 1990). In this study based on a large U.K. population-based sample, none of the reproductive or hormonal potential risk factors studied were found to be associated with acne apart from OCP use. Rather than being causal, this association is likely to be explained by the fact that OCP is one of the therapeutic options for acne. Moreover, in the analyses of discordant dizygotic and monozygotic pairs, OCP use was not significant. Hair thinning (male pattern baldness), which can be a feature of PCO, was not more common in acne twins in this study. The association between acne and raised androgen levels has been controversial as some studies have reported increased levels of both total and free androgens in acne, whereas others have reported androgen levels within normal limits and no correlations between acne severity scores and testosterone levels (Forstrom et al, 1974;Steinberger et al, 1981;Darley et al, 1982;Lucky et al, 1983;Marynick et al, 1983;Schiavone et al, 1983;Ginsberg et al, 1986;Lawrence et al, 1986;Levell et al, 1989;Ramsay et al, 1995). In this study, serum testosterone levels were only available in a very small subset of twins (data not shown) and were not informative because of low power.

PCO linked to acne affects 2–20% of the normal population depending on the definition used and also appears to cluster in families with an autosomal mode of inheritance (Knochenhauer et al, 1998;Franks et al, 1998;Kashar-Miller and Azziz, 1999;Urbanek et al, 1999). Women suffering from PCO not only have high levels of androgens but also insulin resistance with hyperinsulinaemia as well as raised serum lipids. In the twin study reported here, Apo A1 serum levels were lower in acne twins and this is in keeping with lipid changes previously reported in women with PCO (Lithell et al, 1987). This difference in Apo A1 was also found when analyzing acne discordant dizygotic pairs, although this did not reach statistical significance. This difference in Apo A1 between acne subjects and controls needs to be confirmed in other populations and in adolescents. The difference in Apo A1 was not found in the monozygotic acne discordant twin pairs but the number of discordant monozygotic pairs was small. Weight and glucose levels were similar between acne twins and nonacne twins.

In conclusion, this study using the twin model confirms that acne is a highly heritable disease with significant additive genetic effects. The strong genetic basis should stimulate more research leading to gene discovery for this common and often disabling disease. So far, few acne candidate genes have been proposed, some of them related to androgen and steroid metabolism, although sample sizes were small (Blanche et al, 1997;Ando et al, 1998;Munro and Wilkie, 1998;Paraskevaidis et al, 1998;Sawaya and Shalita, 1998). The lack of research in the genetics of acne is surprising considering its incidence, morbidity, and health service costs. Acne is currently treated with keratolytics, topical and systemic antibiotics, anti-androgens as well as topical retinoids, which have different targets with complementary effects on infection, inflammation, sebum secretion rate, and follicular duct keratinization. For severe acne with scarring, oral retinoids have been a major breakthrough in the management of this disease but have significant side-effects with the added concern of teratogenicity. New therapeutic options for all grades of acne, early treatment for genetically susceptible individuals as well as new drugs specifically targeted at genetic pathways would be welcomed. The understanding of the genetics of this common disease may also unravel genes that may have pleiotropic effects on other related phenotypes such as lipid metabolism.

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