title: Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults.
abstract: BACKGROUND
  Phenylalanine 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.
  
  
  METHODS
  Subjects 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).
  
  
  RESULTS
  Analyses 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).
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.forename: Daimei
authors.initials: D
authors.lastname: Sasayama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuo
authors.forename: Anna
authors.initials: A
authors.lastname: Nagashima
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.forename: Sayaka
authors.initials: S
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics / Q000523:psychology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D064368:Healthy Volunteers / Q000523:psychology*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014888:Wechsler Scales; D055815:Young Adult
chemical_list: D010651:Phenylalanine Hydroxylase
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