Variation in the ESR1 and ESR2 Genes and Genetic Susceptibility to Anorexia Nervosa

There is significant evidence for genetic factors in the susceptibility to anorexia nervosa (AN). Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found. In the present study variation in the estrogen receptor 1 (ESR1) and ESR2 genes was examined. Estrogen receptors have been localised to areas of the brain involved in behaviour and regulation of food intake. The anorexic effects of estrogen are accentuated by stress and thus it is postulated that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. A cohort of 170 female, Caucasian AN sufferers and 152 female controls were typed for dinucleotide repeat polymorphisms in both ESR1 and ESR2 and two further SNPs at each locus. Variation at ESR1 was not associated with AN. However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed. Analysis of haplotypes at ESR1 and ESR2 showed no significant evidence of association with AN suggesting that the variability in ESR2 alone may contribute to the genetic susceptibility to AN.