Genetics and the metabolic syndrome

Abstract

Originally coined as “syndrome X” in 1988 by Gerald Reaven (1928), the metabolic syndrome (MetS) encompasses a constellation of risk factors, the coincidence of which amounts to an increased cardiovascular and diabetic risk. Rising numbers of dermatoses are being recognized as cutaneous markers of MetS. Dermatologists should look beyond treating the cutaneous condition and quantify the associated increase in cardiovascular risk. The original dermatosis associated with obesity was acanthosis nigricans—described in 1889 by Paul Gerson Unna (1850-1929) and Sigmund Pollitzer (1859-1937). Over the last 20 years, clear associations between psoriasis, hidradenitis suppurativa, and MetS have also emerged. Several studies have shown synergistic improvement in the cutaneous pathology after treatment of components of MetS. This suggests common causalities and is a burgeoning area of research. We review the available evidence about the genetics underlying psoriasis, hidradenitis suppurativa, and acanthosis nigricans. Despite the strong clinical associations, the underlying genetic basis for a link to MetS remains unclear.

Introduction

The metabolic syndrome (MetS) describes a condition defined by the coexistence of several risk factors that predispose to the development of cardiovascular disease and type 2 diabetes mellitus. The implicated risk factors include the presence of an elevated waist circumference, hypertension (or treatment thereof), dyslipidemia (elevated triglycerides or reduced high density lipoprotein-C), and an elevated fasting glucose.¹ Although the concept remains subject to much debate, revolving around the definitions of each component risk factor, the most recent and unifying diagnostic criteria agree that the presence of three of the five components listed above is sufficient. The growing prevalence of MetS and the gravity of its potential adverse consequences make it an important clinical entity not to be overlooked.

The intrinsic nature of MetS—a clustering of discrete risk factors rather than a single disease entity—translates clinically into a diagnostic dilemma. It requires the coincidence of three conditions, the combination of which varies between individuals. Accordingly, a high index of suspicion is necessary to promote the recognition of MetS. Of interest, there is an accumulating volume of evidence linking certain dermopathies with MetS. In light of this, the putative cutaneous manifestations may come to represent an important screening tool in the future. For dermatologists, this may provide a means of identifying at-risk patients earlier who should be prioritized for further investigation.