Bathum Lise, von Bornemann Hjelmborg Jacob, Christiansen Lene, McGue Matt, Jeune Bernard, Christensen Kaare
Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, DK-5000 Odense C, Denmark.
J Gerontol A Biol Sci Med Sci. 2007 Feb;62(2):196-201. doi: 10.1093/gerona/62.2.196.
Several reports have shown an association between homocysteine, cognitive functioning, and survival among the oldest-old. Two common polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and methionine synthase (MTR 2756A>G) have an impact on plasma homocysteine level.
We examined the effect of the MTHFR 677C>T and MTR 2756A>G genotypes on baseline cognitive functioning, cognitive decline over 5 years measured in three assessments, and survival in a population-based cohort of 1581 nonagenarians. Cognitive functioning was assessed by using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite).
There are no differences in MMSE score (p =.83) or in cognitive composite (p =.56) at intake as a function of genotype tested by analysis of variance, whereas sex and social group have a impact on MMSE (p < or =.03), and social group on the cognitive composite (p <.01). The mean MMSE was lower for women than for men. However, considering the group participating in all three assessments, there were no sex-related differences in MMSE (p =.34). The cognitive decline in the group participating in all three assessments was investigated using regression models for the relationship between cognitive performance and genotype, age, sex, and social group and revealed no significant difference. Furthermore, the MTHFR 677T and MTR 2756A heterozygous and homozygous genotype had no significant impact on survival, with hazard ratios of 1.05 (95% confidence interval [CI], 0.93-1.17), 0.93 (95% CI, 0.77-1.14), 1.05 (95% CI, 0.94-1.18), and 0.97 (95% CI, 0.74-1.28).
MTHFR and MTR genotypes are not associated with cognitive functioning, cognitive decline, or survival among nonagenarians.
多项报告显示，在高龄老人中，同型半胱氨酸、认知功能和生存之间存在关联。编码亚甲基四氢叶酸还原酶（MTHFR 677C>T）和甲硫氨酸合酶（MTR 2756A>G）的基因中的两种常见多态性会影响血浆同型半胱氨酸水平。
我们在一个基于人群的1581名九旬老人队列中，研究了MTHFR 677C>T和MTR 2756A>G基因型对基线认知功能、在三次评估中测得的5年认知衰退以及生存的影响。认知功能通过简易精神状态检查表（MMSE）和五项简短认知测试（认知综合评分）进行评估。
通过方差分析，作为所测试基因型的函数，在入组时MMSE评分（p = 0.83）或认知综合评分（p = 0.56）没有差异，而性别和社会群体对MMSE有影响（p≤0.03），社会群体对认知综合评分有影响（p < 0.01）。女性的平均MMSE低于男性。然而，考虑参与所有三次评估的群体，MMSE不存在性别相关差异（p = 0.34）。使用认知表现与基因型、年龄、性别和社会群体之间关系的回归模型，对参与所有三次评估的群体中的认知衰退进行了研究，结果显示没有显著差异。此外，MTHFR 677T和MTR 2756A杂合子和纯合子基因型对生存没有显著影响，风险比分别为1.05（95%置信区间[CI]，0.93 - 1.17）、0.93（95% CI，0.77 - 1.14）、1.05（95% CI，0.94 - 1.18）和0.97（95% CI，0.74 - 1.28）。
MTHFR和MTR基因型与九旬老人的认知功能、认知衰退或生存无关。
