Abstract
BackgroundPhenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population.MethodsSubjects were 599 healthy adults (166 males and 433 females; mean age 43.8 ± 15.5 years). The Wechsler Memory Scale-Revised (WMS-R) was administered to all participants to assess memory performance. Genotyping was performed for 6 selected tagging SNPs of PAH (rs1722387, rs3817446, rs1718301, rs2037639, rs10860936 and rs11111419).ResultsAnalyses of covariance controlling for sex and education years, indicated a significant association between a SNP (rs2037639) and age-corrected verbal memory index of WMS-R (nominal p = 0.0013) which remained significant after correction for multiple testing ( p = 0.0013 < 0.0017 = 0.05/30tests). Individuals with the GG genotype showed a significantly lower mean verbal memory score, compared with those individuals carrying the AA/AG genotype (106.0 ± 16.0 vs. 111.7 ± 13.4; p = 0.00099). A haplotype block containing two markers of rs2037639 and rs10860936 was associated with verbal memory index (permutation global p = 0.0091).ConclusionsOur findings suggest that common genetic variations in PAH are associated with verbal memory in healthy adults. Unknown functional polymorphisms in PAH or those in other genes nearby might affect memory performance.
Highlights
Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis
We examined whether common genetic variations of PAH are associated with memory performance in Japanese healthy adults
We performed an association study between genetic variations of PAH and memory performance assessed with Wechsler Memory Scale-Revised (WMS-R) in Japanese healthy adults
Summary
Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population. Previous studies [7,8] reported that polymorphisms in PAH confer susceptibility to schizophrenia, a disease characterized by pervasive neurocognitive deficiencies including distinct memory impairment [9], as well as with psychiatric symptoms. Based on these observations, we hypothesized that common genetic variations in PAH might be associated with neurocognitive function, memory performance in particular. There has been no report that examined such an association
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