Genetics seem to be involved in susceptibility to alopecia areata

Alopecia areata hair loss information for men and women
Alopecia Areata 
Alopecia Areata Biology
Alopecia Areata Treatments

  Genetics of Alopecia Areata
 
That alopecia areata could be linked to genetic factors is supported by the fact that in 10% to 20% of the cases the patient’s family reported a family history of this disease. The actual figure could be higher because, often in many mild cases, such information is either neglected or not reported at all. In a study done by Colombe and his colleagues it was seen that, 37% of people who had contracted the disease before the age of thirty had a family history of alopecia areata. The corresponding figure was 7.1% in case of people who were affected after thirty.

There have been a number of cases of twins concurrently affected by this disease. A recent study showed that 6 out of 11 monozygotic twins had concurrent onset of this disease, but none out of 3 zygotic twins had it. Concurrent occurrence of alopecia in both members of a twin is strong evidence of influence of a genetic factor. By and large, it seems alopecia areata is not inherited in a Mendelian way but in a more complex fashion.

Genetic Linkages with HLA Hapolotypes

Many studies have been done on the linkages of various genes to alopecia areata. But the most extensive work has been done on the linkages with the HLA hapolotypes. Less extensive work has also been done on immune response and other genes.

Auto-immune diseases like diabetes mellitus, rheumatoid arthritis have been associated with an increase in hapolotypes. Since alopecia areata is a T-cell mediated autoimmune disease and autoimmunity is associated with HLA-D alleles, researchers have looked for significant linkages between alopecia areata and HLA hapolotypes.

Initial studies did not show any connection between the HLA class I hapolotypes and any antigens. Studies were conducted on two families with a high incidence of alopecia areata. They showed that the affected members had the same class of hapolotype, but the hapolotype was not the same. But this fact does suggest, at least in the case of these two families, the presence of a factor in the MHC gene complex, which could be a determining factor for alopecia areata.

In further studies conducted on two Israeli families no links were found with class I hapolotypes but consistent linkages, were however found with class II hapolotypes. Most of the studies showed an increase in frequency of DR4, DR5 and DR11 antigens. Serological typing techniques showed that DR4 and DR5 antigens were linked to severe types of alopecia areata. DR5 was found to be significantly associated with early and more widespread patchy alopecia. This linkage has been confirmed by molecular typing technique.

Colombe et al observed increase of the broad antigen DQ3 in all their patients. This suggested that DQ3 could be involved in increasing the susceptibility to alopecia areata. A sub-type of DQ3, DQB1*0301 allele which is in linkage disequilibrium with DQ5, was linked to severe alopecia but not to the new patchy disease. DQB1*0301 seems to be a susceptibility marker for all types of alopecia and DQB1*0303 and DRB1*0401 alleles the marker for the severer long-term alopecia totalis and universalis. Recent research has shown association of HLA class I Cw7 with early onset of alopecia areata. These findings lead to the conclusion that a major locus for this disease lies on chromosome 6p.

Gm or immunoglobulin G heavy-chain allotypes, present in chromosome 14, have also been studied. These studies suggest the possibility of involvement of genes on chromosomes 2 or 14. They also show that susceptibility to alopecia areata, is strongly associated with an increase in frequency of Gm 1,2,3,17,5,13,21 and resistance to it, is strongly associated with decrease in frequency of Gm1, 3,17,5,13,21.

Cytokine Genes

Studies by Tallow et al show association between severe alopecia areata and inheritance of allele 2 of the interleukin-1 receptor antagonist gene. This allele is also associated with severe chronic inflammatory disorders including systemic lupus erithematosus and lichen sclerosus. Interleukin-1 is a primary cytokine involved in mediating inflammatory responses. Besides its role in inflammation IL-1 also affects hair growth directly. In hair follicle organ cultures IL-1 inhibits growth of hair fiber and brings about morphological changes that look similar to those observed in alopecia areata.

Allergies

Several studies indicate association between atopic (allergy) diseases and alopecia areata but the findings remain inconclusive. None of the studies used a control group to which the same criteria for defining atropy have been applied. These studies claimed that atopic patients were affected more severely by alopecia areata. However this was not found in a study conducted in India.

Other Genes

Other genes such as tumor necrosis factor, human hairless gene or chromosome 8, CD8 protein or chromosome 2p12, and cacitonin gene related peptide or CGPR have also been studied. Treatment of antigen-presenting cells by CGPR reduces their ability to present antigen. It has been observed that alopecia areata patients have low serum levels of CGPR and give an exaggerated reaction to local injection of CGPR.

Chromosome 21

A case control study threw interesting light on association of alopecia areata with a polymorphism of a human gene MX1 for the interferon induced P78 protein or MxA in the Down syndrome region. It is well known that alopecia occurs commonly in Down syndrome patients. The Down syndrome disease is linked to an additional copy, full or partial, of chromosome 21. It is suspected that the Down syndrome region could have genes involved in the onset of this disease. MX1 is the gene that enables the interferon induced P78 protein or MxA to offer resistance to influenza viruses. This MxA is found to be strongly manifested in affected hair follicles but is absent in normal hair follicles. The case control disease showed significant association of MX1 with alopecia areata. The association was stronger with the milder and patchy alopecia areata.

The case control study just discussed, throws up interesting areas for further investigation of genetic factors responsible for alopecia areata. However, studies to-date locates the site of the major locus, determining alopecia areata, on chromosome 6p.21. although the precise gene causing this disease has not been identified as yet.



  Copyright alopeciaareatainfo