macrophage migration inhibition factor gene sequences are a strong risk factor for early onset of extensive alopecia areata
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Macrophage migration inhibition factor gene sequences are a strong risk factor for early onset of extensive alopecia areata

It is evident to a certain extent that cytokines (chemical signals that cells make and use to communicate with other cells) and certain enzymatic discrepancies play important roles in the pathogenesis of Alopecia areata. When enzymes are involved it is natural that there is involvement at the gene level in the determination of onset and severity of the disease.

In the serum of individuals with inflammatory disorders like asthma, rheumatoid arthritis, acute respiratory distress syndrome, atopic dermatitis and Alopecia areata, there is an increase in the level of MIF [macrophage migration inhibitory factor] in the body. This inhibitory factor is the first reported cytokine that prevents the migration of macrophages. In this case, the MIF cytokine is produced mostly by immune system helper T-cells in response to stimulation by antigens and the function of a macrophage is normally to engulf (“eat”) invading microorganisms and dead cells in the body by phagocytosis to get rid of them. However, macrophages can also work to promote autoimmune diseases. They can eat the damaged tissues, and then use the “digested” tissue to stimulate more immune cells to attack fresh tissue. MIF stimulates the immune system to make other cytokines such as Tumor necrosis factor-alpha and Interleukin-1 to initiate inflammatory disorders so a high level of MIF is probably not good in terms of stopping autoimmune diseases developing.

There are reports from research into other diseases confirming the association and alteration of tetra nucleotide CATT repeats at the -794 nucleotide position in in vitro gene transcription of the MIF gene. Similarly functional polymorphisms in the MIF promoter region have also been identified as a single nucleotide polymorphism in -173 nucleotide position. These defects in the MIF gene may result in its increased expression in disease. It is known that alopecic patients have increased MIF in the serum. And hence a study of these two nucleotide positions at -794 and -173 in the MIF gene was undertaken to see if the same gene defects were present in people with alopecia areata.

The study of MIF in Alopecia areata-

113 Japanese patients [40 men and 73 women] with severe Alopecia areata, but with no family history of the disease, and 194 [115 men and 79 women] healthy controls were selected. The alopecic patients were divided into groups based on their age, onset and the severity of the condition based on SALT score [Severity of ALopecia Tool]. Those patients with 50% hair loss were grouped in a category called S3 and more than 50% in another category called S4. People with Alopecia totalis and Alopecia universalis were referred to as group S5.

Blood samples from all the individuals were obtained and DNA isolated. The MIF gene polymorphism was studied in all the patients. The DNA was processed through various techniques to copy the MIF gene sequence and make lots of copies. This makes it easier to read the gene sequence. The gene sequence was separated using electrophoresis and then the DNA was sequenced using (wait for it) a gene sequencing machine. The DNA sequences are labeled using 4 differently colored fluorescent dyes which each bind to the 4 components of the DNA code – adenosine, cytosine, guanine, and thymine. The sequence is then read by the machine. Gene sequence reading machines are a fairly new development, but they have speeded up genetic research immeasurably. For example – what previously took 4 years to analyze about 100 gene sequences now takes less than 6 months using gene sequencing machines. The results were analyzed statistically to determine whether particular gene sequences were present in people with alopecia areata.

The findings of this study include –

1. The particular gene sequence called MIF-173C was a risk factor for early onset of Alopecia areata.
2. Higher risk and early onset of Alopecia areata was more probable in individuals with GC and CC genotypes than GG genotypes.
3. The gene sequence -794 CATT had no role in any of the Alopecia areata groups studied.
4. Increased frequency of C/7-CATT gene sequences in patient’s early onset of Alopecia areata was observed as compared to the cells with G/5-CATT gene sequences.

The MIF-173*C-CATT7 gene sequence has already been identified in association with development of juvenile idiopathic arthritis and gene sequence CATT -794 with rheumatoid arthritis. Since MIF is secreted by T cells and macrophages in response to inflammatory stimuli and as we already know, T cells have a key role to play in Alopecia areata development, the levels of MIF in the serum in alopecic patients may also be increased by T cell activation. MIF has a homeostatic relation with Tumor necrosis factor-alpha and damage of hair follicles is due to the presence of this and other inflammatory cytokines. Considering all these processes that work in the onset and development of Alopecia areata, it is very clear that MIF may also have a considerable role to play in the process. Extensive Alopecia areata may be due, at least in part, to particular types of gene sequences for the MIF gene.

Macrophage migration inhibition factor gene sequences are a strong risk factor for early onset of extensive alopecia areata references

  • Shimizu T, Hizawa N, Honda A, Zhao Y, Abe R, Watanabe H, Nishihira J, Nishimura M, Shimizu H. Promoter region polymorphism of macrophage migration inhibitory factor is strong risk factor for young onset of extensive alopecia areata. Genes Immun. 2005 Jun;6(4):285-9. PMID: 15815686
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