Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.
The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.
Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yu-Tzu
YT
Chang
Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Shih-Wei
SW
Hsu
Psychiatric Department of Taipei Veterans General Hospital, Taipei, Taiwan.|Psychiatric Division, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Shih-Jen
SJ
Tsai
Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Ya-Ting
YT
Chang
Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chi-Wei
CW
Huang
Psychiatric Department of Taipei Veterans General Hospital, Taipei, Taiwan.
Mu-En
ME
Liu
Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Nai-Ching
NC
Chen
Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Wen-Neng
WN
Chang
Section of Dementia and Cognitive Impairment, Department of Neurology, Chang Gung Memorial Hospital, Linkou, Taiwan.
Jung-Lung
JL
Hsu
Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chen-Chang
CC
Lee
Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chiung-Chih
0000-0002-6721-2556
CC
Chang
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001931:Brain Mapping; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006801:Humans; D021621:Imaging, Three-Dimensional; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D015415:Biomarkers; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
Alzheimer's disease; anatomical structural covariance; default-mode network; genetic effect; posterior cingulate cortex