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11 March 2002

Further studies of genetic susceptibility to Graves' disease in a Russian population.

Mikhail I Balabolkin, Dimitry A Chistiakov, Valery V Nosikov, Rustam I Turakulov

Med Sci Monit 2002; 8(3): CR180-184 :: ID: 420906

Abstract

BACKGROUND: Graves' disease (GD) is a polygenic autoimmune thyroid syndrome.Some of the genes implicated in its pathogenesis may encode thyroid-stimulating hormone receptor (TSHR)and estrogen receptors 1 (ESR1) and 2 (ESR2). We examined dinucleotide repeat polymorphisms in the ESR1and ESR2 genes and D727E amino acid substitution in the TSHR gene for possible association with GD ina Russian population. MATERIAL/METHODS: The polymorphic regions of the target genes were amplified bypolymerase chain reaction (PCR) on the basis of genomic DNA isolated from blood of 78 unrelated Russianpatients with GD and 93 control subjects. To detect the D727E TSHR polymorphism, the PCR product wasadditionally digested with Eco72I restriction endonuclease. The genotype and allele frequencies in thegroups studied were compared by c2 test. The odds ratios and 95% confidence intervals (CI) were calculatedto assess the strength of the relationship between the polymorphisms tested and GD. RESULTS: For polymorphicdinucleotide microsatellites at ESR1 and ESR2, no significant difference was observed in allele frequenciesbetween affected and nonaffected patients. For the D727E TSHR polymorphism, the E allele and the DE genotypewere significantly more frequent (p<0.0001) in patients with GD than in control subjects.
Conclusions: The D727E variant of the TSHR gene is associated with Graves' disease in a Russian population. The E727 allele and the heterozygous D727E genotype are related to higher risk of the disease. No association with GD was found for polymorphic microsatellites of the ESR1 and ESR2.

Keywords: Alleles, Amino Acids, Estrogen Receptor alpha, Estrogen Receptor beta, Genetic Predisposition to Disease, Genotype, Graves, Heterozygote, Microsatellite Repeats, Polymorphism, Genetic, Receptors, Estrogen, Receptors, Thyrotropin, Russia

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750