Further studies of genetic susceptibility to Graves' disease in a Russian population.
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 ESR1 and ESR2 genes and D727E amino acid substitution in the TSHR gene for possible association with GD in a Russian population.


METHODS
The polymorphic regions of the target genes were amplified by polymerase chain reaction (PCR) on the basis of genomic DNA isolated from blood of 78 unrelated Russian patients with GD and 93 control subjects. To detect the D727E TSHR polymorphism, the PCR product was additionally digested with Eco72I restriction endonuclease. The genotype and allele frequencies in the groups studied were compared by c2 test. The odds ratios and 95% confidence intervals (CI) were calculated to assess the strength of the relationship between the polymorphisms tested and GD.


RESULTS
For polymorphic dinucleotide microsatellites at ESR1 and ESR2, no significant difference was observed in allele frequencies between affected and nonaffected patients. For the D727E TSHR polymorphism, the E allele and the DE genotype were 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 gene.
Chistiakov
Dimitry A
DA
INSERM U36, College de France, 121 rue Saint-Jacques, 75231 Paris Cedex 05, France. dimitry.chistiakov@eudoramail.com
Savost'anov
Kirill V
KV
Turakulov
Rustam I
RI
Petunina
Natal'ya
N
Balabolkin
Mikhail I
MI
Nosikov
Valery V
VV
D000328:Adult; D000483:Alleles; D000596:Amino Acids / Q000737:chemistry; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000097:blood / Q000235:genetics; D012426:Russia
D000596:Amino Acids; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D011989:Receptors, Thyrotropin