Keywords: eating disorders; catechol-O-methyltransferase (COMT); polymorphism; haplotype relative risk (HRR); transmission disequilibrium test (TDT)Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. 1 Family and twin studies indicate a significant genetic contribution 2,3 and pharmacological data suggest possible dysfunction of the serotonergic 4,5 and dopaminergic 6-9 pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism 10 and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles. 11 Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% 2 = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemar's 2 = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder. Molecular Psychiatry (2001) 6, 243-245.Fifty-one DSM-IV anorexia nervosa female patients and both their parents were genotyped for the COMT gene (valine to methionine at codon 158) polymorphism. In the light of inherent problems facing association studies, we used the haplotype relative risk (HRR) 12 and the transmission disequilibrium test (TDT) 13 methods that are robust to artifacts caused by population stratification. The genotypes in each family were examined and analyzed so as to determine which of the parents' alleles were transmitted to the affected daughters. The non-transmitted alleles were used to construct the nontransmitted genotypes. According to the HRR method, genotypes and alleles in the patient population are compared with the non-transmitted alleles and genotypes that form the optimal ethnically matched control population. The distribution of the transmitted and non-transmitted genotypes and alleles in the fifty-one trios is presented in Table 1.Homozygotes for the high activity allele (HH) were significantly more frequent among AN patients than in the non-transmitted controls (51% vs 29%, 2 = 4.01, df = 1, P = 0.043; odds ratio: 2.50, 95% CI 1.10-5.64). When allelic distribution was compared, it was found that the high activity allele is significantly more common among patients than in the non-transmitted alleles (68% vs 51%, 2 = 5.20, df = 1, P = 0.023, odds ratio: 2.01, 95% CI 1.39-3.55). The parent population did not differ from the 172 healthy Israeli controls in terms of genotypic and...
Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of human (h) GH in 23 GH deficiency, 8 Turner's syndrome, and 14 intrauterine growth retardation prepubertal patients. They were evaluated before and 1, 3, 6, and 12 months after the onset of hGH treatment. Seven normal children were followed longitudinally as controls. During hGH treatment, a significant increase in muscle tissue and decrease in adipose tissue cross-sectional areas was observed, leading to a dramatic increase in the muscle/adipose tissue cross-sectional area ratio in each period studied. These findings remained highly significant when corrected for the small variation observed in controls. The body mass index was correlated with muscle and adipose tissue cross-sectional area at each time point (P < 0.0001). The muscle cross-sectional area increment correlated with the first year height velocity (P < 0.01). This study indicates that in children with and without GH deficiency, hGH therapy induces rapid and intense variation of muscle and adipose tissue mass, and that magnetic resonance imaging can be used to study some aspects of the metabolic actions of GH.
While enhanced growth velocity is a well-established benefit following the initiation of growth hormone treatment (GHT), the potential benefit of GHT on quality of life (QOL) of short-stature children has not yet been documented. We compare QOL of two groups of short-stature children who attended the Endocrine Unit (EU) and were 2 SD or more below the average for age and gender. The first group included 96 patients of whom 65 were without any underlying disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal disease. These patients were on GHT for at least 2 years. The other group included 33 patients. Owing to lack of resources to include these 33 patients in a clinical trial, they did not get GHT. They were normal variant of short stature, and their height was similar to the height of the 65 children included in the first group. QOL was assessed using self-administered questionnaires, which were filled out by the patients on their regular visit to the EU. QOL was defined in terms of school achievements, leisure activities, emotional and physical self-esteem, relationships with peers and family members. No significant differences were found between the two groups. The mean scores for the different domains of QOL ranged between 2.6 and 3.8 on a scale ranging from 1 (very pessimistic view) to 4 (very optimistic view).
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