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.