Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair bearing sites. Patchy alopecia affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of alopecia areata affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models showed that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified associated with signaling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.

Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.

Female pattern hair loss is a common condition characterized by a diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. The prevalence increases with advancing age. It has been widely thought to be the female counterpart of male balding and is often referred to as female androgenetic alopecia. However, the role of androgens is not fully established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in women but many women with female pattern hair loss have no other clinical or biochemical evidence of androgen excess. Female pattern hair loss is probably a multifactorial genetically determined trait and it is possible that both androgen-dependent and androgen-independent mechanisms contribute to the phenotype. In managing patients with female pattern hair loss the physician should be aware that the adverse effects on quality of life can be quite severe and do not necessarily correlate with the objective degree of hair loss. The treatment options are currently limited but modest improvements in hair density are achievable in some women.

Alopecia areata (AA) is a chronic inflammatory disease characterised by patchy hair loss with T cell infiltration of hair follicles. AA occurs in approximately 0.1% of the general population, but this is increased to 9% in Down syndrome (DS). DS is associated with an additional copy (full or partial) of chromosome 21, and the DS region may potentially include genes involved in the pathogenesis of AA. MX1 is the gene encoding the interferon-induced p78 protein (MxA). MxA protein confers resistance to influenza viruses, and we have previously shown that MxA protein is strongly expressed in lesional anagen hair bulbs from patients with AA but not in normal follicles. We therefore studied the possible involvement of MX1 in the pathogenesis of AA. To establish markers in the MX1 region which could be screened by PCR-based methods, we defined the human MX1 exon/intron organisation and screened the exons and the introns by conformation-sensitive gel electrophoresis. We found that the MX1 gene contains 17 exons extending over 33 kb. The size and sequence of the region from exon 6 to exon 16 are highly conserved between human and mouse. Screening of 4747 bp within the MX1 gene revealed four single nucleotide polymorphisms in intron 6. These polymorphisms are concentrated within 147 bp and show strong linkage disequilibrium. In a case-control association study for the MX1 (+9959) polymorphism in 165 AA patients and 510 controls we found a significant association of this marker with AA (odds ratio 1.79, 95% CI 1.21-2.66, chi2 = 8.464, P = 0.0036). The risk of disease was greater for patchy AA (mild disease) and with early age at onset (odds ratio 2.34, 95% CI 1.24-4.43, P = 0.0072), providing new evidence of genetic heterogeneity in AA. Our demonstration of genetic association between the MX1 gene and disease supports the hypothesis that this is a new candidate gene in AA.