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.

Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa.

Previous studies have demonstrated aberrant expression of serotonin in individuals with an eating disorder. Given this the serotonin transporter gene (5-HTT) is a strong candidate to contribute to the genetic component of the aetiology of eating disorders. To determine the role of this particular gene in the susceptibility to anorexia nervosa (AN) we have examined a tandemly repeated sequence close to the promotor region of the 5-HTT gene, which is represented by a long (L) and short (S) variant. Previous studies have shown that the transcriptional activity of the 5-HTT gene differs significantly between these two alleles. A group of 138 Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria AN patients and 90 controls were genotyped at the 5-HTT gene linked polymorphism (5-HTTLPR). Statistical analysis showed no significant difference in allele or genotype frequencies between the two groups. These data suggest that there is no association between 5-HTTLPR genotype and susceptibility to AN, in our population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:53-55, 2000.

Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa.

Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome.

Fine mapping of the human 5-HTR2a gene to chromosome 13q14 and identification of two highly polymorphic linked markers suitable for association studies in psychiatric disorders.

The serotonergic system is known to play an important role in a number of psychiatric disorders. Indeed, treatments involving agents that have their pharmacological activities within this system are the mainstay of treatment for disorders such as schizophrenia. It is now widely accepted that many common psychiatric disorders have a familial or genetic component and as a result of this there has been an upsurge in interest in the 5-hydroxytryptamine (5-HT) pathways. A number of groups have attempted to establish whether polymorphism in particular proteins of the serotonergic system may form part of the genetic component of psychiatric disorders, including schizophrenia and anorexia nervosa. However, the data from these studies are conflicting and the problem is compounded by the lack of known polymorphic genetic markers mapping in close proximity to genes encoding proteins envolved directly or indirectly in 5-HT neurotransmission. In the current study, we have fine mapped the gene for 5-HTR2a by radiation hybrid mapping, and we report two new, highly linked, polymorphic markers that are suitable for linkage and association studies.

Scottish survey of chronically ill day patients: 3-year follow-up.

Chronically ill day patients were followed up 3 years after identification in the catchment areas of 13 psychiatric hospitals serving 54% of the Scottish population. Five per cent had died, 6% were in-patients, 56% remained day patients and 14% were supported by community psychiatric nurses or attended an out-patient clinic; contact had been lost with 19%. Over 3 years, 32% had had at least one admission to in-patient care; a wide range of other services was also used. There was little change in the level of disability; a typical patient in contact at follow-up was single, schizophrenic, and rather disabled.