Abstract
A common single nucleotide polymorphism (SNP) in the gene encoding catechol-O-methyltransferase (COMT), Val158Met, is thought to influence cognitive performance due to differences in prefrontal dopaminergic neurotransmission. Previous studies lend support for the hypothesis that the “at risk” genotype comprising two Val-alleles (low dopamine) might benefit more from plasticity-enhancing interventions than carriers of one or two Met-alleles. This study aimed to determine whether the response to dietary interventions, known to modulate cognition, is dependent on COMT genotype. Blood samples of 35 healthy elderly subjects (61.3 years ±8 SD; 19 women, 16 men, BMI: 28.2 kg/m2 ±4 SD) were genotyped for COMT Val158Met by standard procedures (Val/Val = 6; Val/Met = 20; Met/Met = 9). Subjects had previously completed a randomized controlled trial investigating the effects of caloric restriction (CR) or enhancement of unsaturated fatty acids (UFA) on immediate and delayed verbal recognition memory. Homozygous Val/Val-carriers had significantly lower memory scores than Met-carriers at baseline (p < 0.001). Significant interactions of genotype and dietary intervention with regard to cognition were found: CR- and UFA enhancement-induced memory improvements of Val/Val-carriers were considerably greater than those of Met-carriers (ANOVA p's < 0.02). The current study shows for the first time that cognitive effects of dietary interventions are dependent on COMT Val158Met genotype. Our findings lend further support to the hypothesis that an “at risk” genotype might benefit more from plasticity-enhancing interventions than the “not at risk” genotype. This might help to develop individualized therapies in future research based on genetic background.
Highlights
Previous studies reported genotype-associated variations in both brain functions and physiology for a common single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene, leading to a substitution of valine (Val) to methionine (Met) at the codon 158 on chromosome 22q11 (Val158Met; Goldberg and Weinberger, 2004)
Significant interactions of genotype and dietary intervention with regard to cognition were found: caloric restriction (CR)- and unsaturated fatty acids (UFA) enhancement-induced memory improvements of Val/ Val-carriers were considerably greater than those of Met-carriers (ANOVA p’s < 0.02).The current study shows for the first time that cognitive effects of dietary interventions are dependent on COMT Val158Met genotype
Genetic analysis of COMT Val158Met genotype revealed a distribution of 6 Val/Val-carriers (CR: n = 3, UFA: n = 3) and 29 Metcarriers (CR: n = 13, UFA: n = 14)
Summary
Previous studies reported genotype-associated variations in both brain functions and physiology for a common single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene, leading to a substitution of valine (Val) to methionine (Met) at the codon 158 on chromosome 22q11 (Val158Met; Goldberg and Weinberger, 2004). Homozygous carriers of the Val-allele performed worse in executive and memory tasks than carriers of the Met-allele (Egan et al, 2001; Meyer-Lindenberg et al, 2006; Raz et al, 2009). This differential cognitive performance might depend on a higher activity of the Val-encoded COMT enzyme (Lotta et al, 1995), playing a unique role for degradation of dopamine in the prefrontal cortex (PFC) (Mattay et al, 2003). The impact of COMT genotype on cognition is supposed to magnify during late adulthood (Diaz-Asper et al, 2006; Lindenberger et al, 2008). Negative results have been reported as well (Potter et al, 2009), and the impact of COMT genotype on cognition is still a matter of debate (Barnett et al, 2008; Goldman et al, 2009)
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