X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case-control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.
Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. olfa.khalifa@inserm.fr.|University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France. olfa.khalifa@inserm.fr.
Olfa
O
Khalifa
Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. ympers2000@yahoo.fr.|University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France. ympers2000@yahoo.fr.|Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France. ympers2000@yahoo.fr.
Yves-Marie
YM
Pers
Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France. rosannaferreiralopez@gmail.com.
Rosanna
R
Ferreira
Inserm, U1051, Institute for Neurosciences Montpellier, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. audrey.senechal@inserm.fr.
Audrey
A
Sénéchal
Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. christian.jorgensen@inserm.fr.|University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France. christian.jorgensen@inserm.fr.|Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France. christian.jorgensen@inserm.fr.
Christian
C
Jorgensen
Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. florence.apparailly@inserm.fr.|University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France. florence.apparailly@inserm.fr.|Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France. florence.apparailly@inserm.fr.
Florence
F
Apparailly
Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France. isabelle.richard@inserm.fr.|University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France. isabelle.richard@inserm.fr.
Isabelle
I
Duroux-Richard
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D041321:Chromosomes, Human, X; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D012737:Sex Factors
D051858:Forkhead Transcription Factors; D035683:MicroRNAs; C418974:FOXP3 protein, human; C525709:MIR221, human; C525710:MIR222, human; C585583:MIRN532 microRNA, human; C546084:MIRN98 microRNA, human
FoxP3; X-chromosome; gender; miRNA; rheumatoid arthritis