Behav Brain Funct. 2013 Jul 30;9:30. doi: 10.1186/1744-9081-9-30.

Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults.


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.


必須アミノ酸であるフェニルアラニンを代謝するフェニルアラニン水酸化酵素(PAH)は、カテコールアミンの合成に必要である。 PAHの稀な変異型は、常染色体劣性遺伝疾患のフェニルケトン尿症(PKU)の原因であり、それは知的障害を含む精神神経症状を合併する。今回我々は、日本人のサンプルを用い、PAHのSNPと記憶機能の関連について検討した。対象は599人の健康成人(男性166人、女性433人、平均年齢43.88±15.5歳)で、記憶機能評価にはウエクスラー記憶検査(WMS ?R)を用いた。PAHのタグSNP ( rs1722387 、 rs3817446 、 rs1718301 、 rs2037639 、 rs10860936とrs11111419 )のジェノタイピングを行った。rs2037639と言語記憶との間に有意な関連がみられた(性と年齢を補正した共分散分析:p = 0,0013, ボンフェローニ補正:p = 0,0013 < 0,0017 =0,05/30tests)。GG型は、AA 型とAG型よりも言語記憶が有意に低下していた(p = 0,00099 )。rs2037639とrs10860936を含むハプロタイプは、言語記憶と有意に関連していた(global p = 0,0091)。今回の知見は、健康成人において、PAHのコモンSNPが言語記憶と関連していることを示唆している。PAHもしくはその近隣の未知の機能的SNPが記憶機能に影響を与えている可能性がある。

DOI:  23898865