Sporadically, I see questions on LN about thyroid and autoimmune
disease...this article might be of interest to those of us who run across
thyroid issues regularly:
The <Public Health> MEDLINEŽ citation of the week -- Cytokine gene
polymorphisms in autoimmune thyroid disease. Hunt PJ, Marshall SE, Weetman
AP, Bell JI, Wass JA, Welsh KI Department of Endocrinology' Radcliffe
Infirmary' Oxford' United Kingdom.; J Clin Endocrinol Metab; 2000 May;
85(5):1984-8
PURPOSE: Susceptibility to the autoimmune thyroid diseases' Graves' disease
(GD) and autoimmune hypothyroidism (AIH)' depends on a complex interaction
between environmental and genetic factors. The human leukocyte antigen and
cytotoxic T lymphocyte-associated-4 regions appear to influence
susceptibility to disease' but the effect is not major' and the other genes
remain unknown. Cytokines are crucial in the regulation of immune and
inflammatory responses and therefore are potential candidate genes for
autoimmune thyroid disease. In a case-control study' using a unified method
of genotyping' we have examined 15 polymorphisms in 9 cytokine genes in 215
patients with autoimmune thyroid disease (GD' 138; AIH' 77) and 101 normal
controls. Polymorphisms in the genes for interleukin-1alpha (IL-1alpha)'
IL-1beta' IL-1 receptor antagonist' IL-1 receptor 1' IL-4' IL-4 receptor'
IL-6' IL-10' and transforming growth factor-beta were investigated.
Genotyping was performed using the PCR and!
sequence-specific primers. Analysis showed a reduced frequency of the
variant t allele in the IL-4 promoter polymorphism (position 590) in
patients with GD and in the entire patient group (GD and AIH) compared with
the control group [corrected P (Pc) = 0.00004 and Pc < 0.00001 for GD and
all patients' respectively]. This was reflected in a reduction in the
heterozygote genotype in the patient groups compared to the controls [c/t
heterozygotes GD' 12%; Pc = 0.06' odds ratio' 0.4 (95% confidence interval'
0.2-0.7); all patients' 11%; Pc = 0.008; odds ratio' 0.4 (95% confidence
interval' 0.2-0.7); control subjects' 23%]. There were no significant
differences between the study groups for the other polymorphisms examined'
and subgroup analysis revealed no association with clinical parameters of
disease. These results suggest that an IL-4 variant or a closely linked gene
has a modest protective effect against the development of autoimmune thyroid
disease' particularly GD. This vari!
ation in the IL-4 gene may provide further clues to the pathogenesis of
autoimmune thyroid disease and other organ-specific autoimmune diseases.
Furthermore' these results suggest that subtle variation in immunoregulatory
genes may be associated with autoimmune disease states.
Chris Hafner-Eaton, PhD, MPH, CHES, IBCLC [log in to unmask]
mom, wife, educator, lactation consultant, researcher, scientist, author,
organic gardener, photographer, lapidary creator, lousy cleaner.
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