Association of Eating Disorders with Catechol-<i>O</i>-Methyltransferase Gene Functional Polymorphism

Abstract

Aim: The aim of this study was to evaluate functional catechol-O-methyltransferase (COMT) genetic variation as a risk factor for eating disorders (ED). Method: Eighty women receiving treatment for serious ED (52 for anorexia nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low-activity allele and the high-activity allele (H) were determined. Results: The H/H genotype was twice as frequent in the ED group as in the control group (52.5% in the ED group and 25% in controls, χ² = 15.5, d.f. = 2, p < 0.001, odds ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients (χ² = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio = 4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison to 47.8% of patients from the control group (χ² = 13.89, p < 0.001, odds ratio = 6.088). In the anorexia group, H allele frequency was enhanced even higher (70.2 vs. 47.8%, χ² = 14.48, p < 0.001, odds ratio = 8.175). The genotype associations in the subgroup of bulimia patients were not significant, but a trend for a higher frequency of the H allele was found (p = 0.084, odds ratio = 5.309). Conclusions: These findings seem to suggest that a turnover of catecholamines, connected with polymorphism determining high activity of COMT enzyme, is connected with the risk of ED occurrence, particularly anorexia nervosa. The risk is significantly higher for women with an allele of higher activity.

Catechol-O-methyltransferase activity in erythrocytes from patients with eating disorders

“…The lack of a significant difference between patients with AN and control group is in line with several studies on literature, which also reported no association between COMT polymorphism and AN [1,2,15,16,18]. However, an association between Val158 and AN was also shown in two studies [9,10]. Curiously, a study of Michaelovsky et al [30] showed that Val158 was associated with restricting AN and the Met158 had protective effect.…”

“…The results were controversial: some studies appointed the higher activity allele as risk factor for AN [9,10] or BN [1,11,12], whereas other group of studies pointed out the lower activity COMT allele [13,14]. Some studies did not find association between this polymorphism and AN [1,2,[15][16][17][18] and BN [10].…”

Genetics and epigenetics of eating disorders

“…101 In the case of AN, no association between DRD4 and BMI has been reported. 102 In BN, studies have yielded mixed results regarding the overtransmission of catechol-O-methyltransferase ( COMT ) rs4680 variants, 103,104 and a meta-analysis of eight case-control studies failed to find an association between rs4680 and AN susceptibility. 105 …”

Genetic Susceptibility to Eating Disorders: Associated Polymorphisms and Pharmacogenetic Suggestions

“…The 158Val allele is responsible for high enzymatic activity, which is approximately four-times greater than the 158Met allele [100]. A nominal association of the ValVal genotype and the Val allele with AN has been shown in two studies [101,102] but not confirmed in a large case-control study of individuals form six European countries [103]. Similarly, a preferential transmission of the Val allele was detected in a sample of 66 ANR trios, but not confirmed in a larger study including 372 AN trios (Table 1) [103].…”