Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome

Journal of Translational Medicine

Research

Kaixiong Ye¹  Alon Keinan¹  Arnaud Germain²  Maureen R. Hanson²  Paul Billing-Ross³  Zhenglong Gu³ 

[1] Department of Biological Statistics and Computational Biology, Cornell University, 14853, Ithaca, NY, USA;Department of Molecular Biology and Genetics, Cornell University, 14853, Ithaca, NY, USA;Division of Nutritional Sciences, Cornell University, 14853, Ithaca, NY, USA;

关键词: Myalgic encephalomyelitis (ME);    Chronic fatigue syndrome (CFS);    Next-generation sequencing;    Mitochondrial DNA;    mtDNA;    Heteroplasmy;    Association;    SNPs;    Haplogroup;    Variants;   

DOI  :  10.1186/s12967-016-0771-6

 received in 2015-10-14, accepted in 2016-01-05,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMitochondrial dysfunction has been hypothesized to occur in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a disease characterized by fatigue, cognitive difficulties, pain, malaise, and exercise intolerance. We investigated whether haplogroup, single nucleotide polymorphisms (SNPs), or heteroplasmy of mitochondrial DNA (mtDNA) were associated with health status and/or symptoms.MethodsIllumina sequencing of PCR-amplified mtDNA was performed to analyze sequence and extent of heteroplasmy of mtDNAs of 193 cases and 196 age- and gender-matched controls from DNA samples collected by the Chronic Fatigue Initiative. Association testing was carried out to examine possible correlations of mitochondrial sequences with case/control status and symptom constellation and severity as reported by subjects on Short Form-36 and DePaul Symptom Questionnaires.ResultsNo ME/CFS subject exhibited known disease-causing mtDNA mutations. Extent of heteroplasmy was low in all subjects. Although no association between mtDNA SNPs and ME/CFS vs. healthy status was observed, haplogroups J, U and H as well as eight SNPs in ME/CFS cases were significantly associated with individual symptoms, symptom clusters, or symptom severity.ConclusionsAnalysis of mitochondrial genomes in ME/CFS cases indicates that individuals of a certain haplogroup or carrying specific SNPs are more likely to exhibit certain neurological, inflammatory, and/or gastrointestinal symptoms. No increase in susceptibility to ME/CFS of individuals carrying particular mitochondrial genomes or SNPs was observed.

【 授权许可】

CC BY   
© Billing-Ross et al. 2016