Insulin-Like Growth Factor-I Gene Polymorphism in Acne Vulgaris

Abstract

Summary and conclusion A cne vulgaris is a multifactorial inflammatory skin disease of the pilosebaceous follicle, caused by both host and environmental factors and microbial components. The pathogenesis of acne is thought to involve an interplay between a number of factors , including excess androgenic stimulation and sebum hypersecretion, abnormal differentiation, proliferation and hyperkeratinization of the epidermal keratinocytes, especially those lining the duct region of the sebaceous unit. All these processes lead to occlusion of the follicular orifice by a plug containing mostly a mixture of keratin and dead skin cells, together with sebum, hypercolonization by the bacterium Propionibacterium acnes, and the appearance of early skin symptoms called comedos. In later stages, the lesions and the surrounding tissues can become inflamed, and papules, pustules or, in more severe cases, nodules and cysts can develop. The severity of the inflammatory reaction and the subsequent acne symptoms vary considerably in the affected subjects, in part because of individual genetic susceptibility factors. Several studies have shown that elevated levels of serum insulin-like growth factor-I (IGF-I) correlate with overproduction of sebum and acne. It has recently been shown that IGF-I can increase lipid production in sebocytes in vitro via the activation of IGF-1 receptor through multiple pathways. The first molecular genetic analyses of a genetic predisposition to acne were performed only in the 1990s, and since that time only a small number of publications have emerged. Most of the genes studied so far are either key players of innate immune events during lesion formation or have a function in steroid hormone metabolism; recently additional polymorphisms and mutations that can be linked to cellular metabolic processes have been published. Recently, a polymorphism in the promoter of the IGF-I gene has been reported. This polymorphism consists of a highly polymorphic microsatellite composed of variable cytosine adenosine (CA) repeats situated in the promoter region 1-kb upstream from the transcription site of IGF-I. The number of (CA) repeats ranges between 10 and 24, with the most common allele containing 19 (CA) repeats in the Caucasian population. There is a functional relationship between IGF-I (CA) polymorphism and circulating IGF-1 levels. Carriers of the 192 bp allele and ⁄ or 194 bp allele of the IGF-1 promoter have higher circulating IGF-1 levels than non-carriers. These polymorphism may directly influence the expression of IGF-I. The aim of our study was to investigate the presence of IGF-I (CA) polymorphism in the pathogenesis of acne among two studied groups of twenty patients with untreated acne vulgaris and another twenty healthy age matched persons as controls. As regard results, this study revealed that there was highly statistically significant difference between the two studied groups regarding ILGF1 (CA) 19 polymorphism and also a highly statistically significant difference between them regarding DNA concentration.