Linkage and association analysis of genes encoding cytokines and myelin proteins in multiple sclerosis.
Several genetic factors are likely to play a role in the etiology of multiple sclerosis (MS). We used a candidate gene strategy in a study of polymorphic markers within or close to genes encoding cytokines (interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-4 receptor (IL-4R), IL-10, transforming growth factor-beta1 and -beta2) and myelin proteins (2',3'-cyclic-nucleotide 3'-phosphohydrolase (CNP:ase), myelin associated glycoprotein, oligodendrocyte myelin glycoprotein, proteolipid protein) in 34 Swedish multiplex MS families and in 147 sporadic MS patients and 95 healthy controls. No evidence for linkage was observed in two-point linkage analysis. However, a slightly positive LOD score of 0.88 (theta = 0.01) for IFN-gamma was found. Affected pedigree member (APM) analysis indicated a possible linkage with TGF-beta2 (p = 0.008) and IL-4R (p = 0.043). None of the cytokine markers were associated with MS in case-control analysis. Our results suggest a possible importance of the TGF-beta2, IL-4R and IFN-gamma genes in MS.
He
B
B
Department of Neurology, Huddinge University Hospital, Karolinska Institute, Sweden. bing.he@cnsf.ki.se
Xu
C
C
Yang
B
B
Landtblom
A M
AM
Fredrikson
S
S
Hillert
J
J
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005192:Family Health; D058851:GPI-Linked Proteins; D008040:Genetic Linkage; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000235:genetics; D018992:Myelin-Associated Glycoprotein / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein; D011110:Polymorphism, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D016207:Cytokines; D058851:GPI-Linked Proteins; D007376:Interleukin-2; C571326:MOG protein, human; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C560528:OMG protein, human; D019948:Receptors, Interleukin-4; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases