viser, at mennesker med Myalgisk encephalomyelitis (ME) har variationer i deres DNA 8 forskellige steder.
Ved at sammenligne DNA fra 15.579 ME patienter med DNA fra kontrolpersoner blev de 8 områder i DNAet afsløret som signifikant for ME patienterne.
I disse områder findes følgende gener, som kan være relateret til ME sygdomsmekanismen:
BTN2A2 - butyrophilin subfamily 2 member A2
CA10 - carbonic anhydrase 10
CCPG1 - cell cycle progression 1
FBXL4 - F-box and leucine rich repeat protein 4
OLFM4 - olfactomedin 4
RABGAP1L - RAB GTPase activating protein 1 like
SUDS3 - SIN3A corepressor complex component SDS3
Betydning af ændringer i DNAet
En variation i et gen kan medføre, at der er en øget eller nedsat ekspression af genet. I figur 4 i artiklen er det angivet, hvad man kan formode gen-variationerne betyder for ekspression af ovennævnte gener. De grønne cirkler angiver øget ekspression og de blå cirkler viser nedsat ekspression.
Fig. 4 fra reference 1: Approximate Bayes factor posterior probability (PPH4) that mRNA expression and ME/CFS traits are associated and share a single causal variant. Thirty-four protein coding genes (y-axis) with at least one expression QTL (eQTL; GTEx-v10) within a FUMA-defined ME/CFS interval that show colocalisation with the eQTLs for at least one of 49 GTEx-v10 tissues (x-axis). Green circles indicate that increased ME/CFS risk allele is associated with increased gene expression for eQTLs in the FUMA-defined interval. Blue circles indicate that increased ME/CFS risk allele is associated with decreased gene expression for eQTLs in the FUMA-defined interval, and vice-versa. The area of each circle indicates the test’s value of PPH4 (posterior probability for single shared causal variant): smaller circles indicate 0 < PPH4 < 0.75, and larger ones indicate PPH4 ≥ 0.75.
Vigtige oplysninger fra artiklen
Nedenstående findes i citatform nogle vigtige oplysninger fra artiklen:
"Complexes involving
butyrophilin-3 and -2 homologues (BTN3A1, BTN3A2, BTN3A3, BTN2A1 and BTN2A2) allow
innate-like Vγ9Vδ2 T cells to distinguish self-derived from non-self-derived pyrophosphate
antigens (pAgs) (47). Mouse Btn2a2 knockout model phenotypes (48,49) – together with the
discordance of BTN2A2 expression and ME/CFS risk effects (Fig. 4) – imply that the ME/CFS
risk-increasing allele could impair T-cell responses and worsen autoimmune disease."
"The
CA10 protein inhibits the addition of heparan sulfate glycosaminoglycan to presynaptic
neurexins. This post-translation modification enables their binding to postsynaptic
neuroligins
(52,53). This trans-synaptic interaction is critical for synaptic transmission and,
when disrupted in a rodent model, prevents pain (54)."
"CCPG1 mediates the
selective degradation of the endoplasmic reticulum by autophagy (62). This is a host
defense mechanism when pathogens infect cells, and its deficiency facilitates viral infection
(63)."
"Mutations in FBXL4 cause increased mitophagy, and
mitochondrial DNA depletion (60)."
"Olfactomedin-4 (OLFM4) suppresses antibacterial and inflammatory responses by binding to neutrophil cationic proteins and neutralises their
ability to kill bacteria and form immunogenic complexes with DNA (61)."
"RABGAP1L promotes expulsion of the bacterium Streptococcus pyogenes from cells via
endocytosis (45) and also limits replication of multiple viruses (46). The ME/CFS risk
increasing allele is associated with decreasing RABGAP1L gene expression for GTEx-v10
eQTLs in the FUMA-defined interval, and vice-versa (Fig. 4). This suggests that ME/CFSassociated RABGAP1L variants could enhance susceptibility to bacterial and viral infection."
"SUDS3 encodes a protein that is a negative regulator of
microglial inflammation (51). ME/CFS genetic risk at this locus, therefore, could act to
suppress the microglial inflammatory response."
"Three of the most likely genes produce proteins that respond to an infection.
Another likely gene is related to chronic pain. None are related to depression or anxiety."
"Our findings suggest that both immunological and
neurological processes are involved in the genetic risk of ME/CFS."
Reference:
Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome
