Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults.
Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults.
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DOI：
10.1186/1744-9081-9-30
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发表时间：
2013-07-30
期刊：
影响因子：
--
通讯作者：
Kunugi H
中科院分区：
文献类型：
--
作者：
Teraishi T;Sasayama D;Hori H;Yamamoto N;Fujii T;Matsuo J;Nagashima A;Kinoshita Y;Hattori K;Ota M;Fujii S;Kunugi H
苯丙氨酸羟化酶 (PAH) 是代谢苯丙氨酸的酶，苯丙氨酸是儿茶酚胺合成所需的必需氨基酸。 PAH 的罕见突变是苯丙酮尿症 (PKU) 的病因，苯丙酮尿症是一种常染色体隐性遗传疾病，其特征是神经精神症状，包括智力障碍。我们研究了日本人群中 PAH 的常见单核苷酸多态性 (SNP) 与记忆表现之间是否存在关联。受试者为 599 名健康成年人（166 名男性和 433 名女性；平均年龄 43.8±15.5 岁）。对所有参与者进行韦克斯勒记忆量表修订版（WMS-R）以评估记忆表现。对 PAH 的 6 个选定的标记 SNP（rs1722387、rs3817446、rs1718301、rs2037639、rs10860936 和 rs11111419）进行基因分型。控制性别和教育年限的协方差分析表明，SNP (rs2037639) 与 WMS-R 的年龄校正言语记忆指数 (标称 p = 0.0013) 之间存在显着关联，在多次测试校正后，该关联仍然显着 (p = 0.0013 < 0.0017 = 0.05/30 次测试)。与携带 AA/AG 基因型的个体相比，具有 GG 基因型的个体表现出显着较低的平均言语记忆得分（106.0±16.0 vs. 111.7±13.4；p=0.00099）。包含 rs2037639 和 rs10860936 两个标记的单倍型块与言语记忆指数相关（排列全局 p = 0.0091）。我们的研究结果表明，PAH 的常见遗传变异与健康成年人的言语记忆有关。 PAH 或附近其他基因中未知的功能多态性可能会影响记忆能力。
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. 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). 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). 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.
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