Genetic predisposition to the development of diffuse toxic goiter in the population of Moscow

Thyroid pathology ranks first in the incidence of endocrine diseases (0.5% of the general population), by passing ahead of even diabetes mellitus (0.4%). The most common thyroid diseases include diffuse toxic goiter (DTG) - Graves' disease. In this study, polymorphic markers were developed for some possible gene candidates and the association of these markers with the development of DTG was studied in a Russian population. A group of 78patients with DTG and a group of 153 healthy volunteers were examined. Examining the association of the polymorphic microsatellite markers D6S2414 and D6S1271 located on chromosome 6 amongst the genes of the major histocompatibility complex (MNS locus) indicated that both markers are associated with DTG.

The use of the polymorphic marker Ala 17Thr of a cytotoxic T-lymphocytic serine esterase gene (CTLA4) also could detect the marked association of this marker with DTG. The allele Ala and the genotype Ala/Ala increase a risk for the pathology (OR = 2.94 and 3.57, respectively) whereas the carriage of the allele Thr and particularly its homozygosis are linked with a lower risk for DTG (the relative risk (RR) is 0.34 and 0.28, respectively). In case of the polymorphic marker His60Arg if the gene encoding for the /3-subunit of a large multifunctional proteosome (LMP2), there was no association with DTG in a Moscow population. Comparing the distribution of the alleles and genotypes of the polymorphic minisatellite marker arranged in the intron 2 of an interleukin-1 receptor antagonist gene in the groups of healthy volunteers and patients with DTG showed significant differences in the occurrence of allele 2 and gen­otypes 2/4 and 4/4. Thus, the findings suggest that the MNS locus, the cytotoxic T-lymphocytic serine esterase gene (CTLA4), and the interleukin-1 receptor antagonist gene (IL1RN) play an important role in the development of DTG in the population of Moscow.

diffuse toxic goiter, gene candidates, polymorphic markers, Moscow Russian population

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