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Neurobiol Aging. 2019 May 23. pii: S0197-4580(19)30166-6. doi: 10.1016/j.neurobiolaging.2019.05.013. [Epub ahead of print]

One-carbon metabolism gene polymorphisms are associated with cognitive trajectory among African-American adults.

Author information

1
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA. Electronic address: baydounm@mail.nih.gov.
2
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA.
3
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA; Department of Psychology, University of Maryland Baltimore County, Catonsville, MD, USA.
4
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Abstract

The sex-specific link between longitudinal annual rate of cognitive change (LARCC) and polymorphisms in one-carbon metabolism enzymatic genes remains unclear, particularly among African-American adults. We tested associations of 14 single nucleotide polymorphisms (SNPs) from MTHFR, MTRR, MTR, and SHMT genes and select MTHFR haplotypes and latent classes (SNPHAP/SNPLC) with LARCC. Up to 797 African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (age: 30-64 y, 52% women) had 1.6-1.7 (i.e., 1 or 2) repeated measures (follow-up time, mean = 4.69 y) on 9 cognitive test scores, reflecting verbal and visual memory, verbal fluency, psychomotor speed, attention, and executive function: California Verbal Learning Test-immediate recall (CVLT-List A), CVLT-DFR (delayed free recall), Benton Visual Retention Test (BVRT), Animal Fluency (AF), Digits Span Forward and Backward tests, and Trail Making Test parts A and B (Trails A and B). Multiple linear mixed-effects and multiple linear regression models were conducted. Overall, MTHFR SNPs rs4846051(A1317G, G>A) and rs1801131(A1298C, G>T) were associated with slower and faster declines on AF, respectively, whereas rs2066462(C1056T, A>G) was related to slower decline on Trails B (executive function). Among men, rs4846051(A1317G, G>A) was linked to faster decline on BVRT (visual memory), whereas rs2066462(C1056T, A>G) and rs9651118(C>T) were associated with slower decline on CVLT-List A and rs9651118(C>T) with faster decline on CVLT-DFR. Among women, a slower decline on the domain "verbal memory/fluency" was observed with rs1801133(C677T, A>G). MTHFR2SNPHAP [rs1801133(C677T, A>G)/rs1801131(A1298C, G>T): GG] was associated with slower decline on AF among women, whereas MTHFR3SNPHAP(AT) was linked with slower decline on CVLT-List A among men but faster decline on "verbal memory/fluency" among women. Similar patterns were observed for MTHFR SNPLCs. In sum, MTHFR gene variations can differentially impact longitudinal changes in multiple cognitive domains among African-American adults.

KEYWORDS:

Aging; Cognitive change; Genetic polymorphisms; Haplotypes; MTHFR; One-carbon metabolism

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