X chromosome inactivation in females with multiple sclerosis.
The aetiology of multiple sclerosis (MS) is unknown. Autoimmune mechanisms are most probably involved. Loss of immunological tolerance to self-antigens is a common feature of autoimmune disorders. Response to X-linked self-antigens could be influenced by X-chromosome inactivation, and contribute to the gender bias observed in autoimmune disorders. Previous studies have indicated an association between skewed X inactivation and autoimmune thyroid disease and scleroderma. To investigate a potential role of X inactivation in MS, we compared the X-inactivation pattern in 568 female MS patients with controls. We found no difference in degree of skewing between patients (median 64%) and controls (median 65%) (P = 0.474). The X-inactivation pattern did thus not explain the female predominance of MS patients in general. As the aetiology of different subgroups of MS may differ, patients were grouped according to disease course: relapsing-remitting (RR-MS), secondary progressive (SP-MS) and primary progressive (PP-MS). A comparison of the X-inactivation pattern between subgroups indicated a possible difference in degree of skewing between patients with a progressive versus a relapsing course (P = 0.05).
Knudsen
G P S
GP
Department of Medical Genetics, Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway. gunpeggy@knudsen.as
Harbo
H F
HF
Smestad
C
C
Celius
E G
EG
Akesson
E
E
Oturai
A
A
Ryder
L P
LP
Spurkland
A
A
Ørstavik
K H
KH
D000328:Adult; D000367:Age Factors; D000368:Aged; D003627:Data Interpretation, Statistical; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000235:genetics*; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics; D012737:Sex Factors; D049951:X Chromosome Inactivation / Q000235:genetics*