期刊
GENES AND IMMUNITY
卷 6, 期 2, 页码 153-161出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gene.6364164
关键词
multiple sclerosis; gender; interferon gamma (IFNG); polymorphisms; association
资金
- NIMH NIH HHS [MH-56207] Funding Source: Medline
- NINDS NIH HHS [NS45442] Funding Source: Medline
Interferon-gamma (IFNgamma) treatment is deleterious in multiple sclerosis ( MS). MS occurs twice as frequently in women as in men. IFNg expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CA(n)],a single nucleotide polymorphism 3' of IFNG [3'(325)* G --> A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3'(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P = 0.044; OR: 2.58, 95% CI: 0.97-8.08) and Northern Ireland (P = 0.019; OR: 2.37, 95% CI: 1.10-5.13). There is a nonsignificant trend in the same direction in Belgian men (P = 0.299; OR: 1.50, 95% CI: 0.71-3.26). Men carriers of I1(761)*CA(13), which is in strong linkage disequilibrium with the 3'( 325)* A, have increased susceptibility (P = 0.050; OR: 2.22, 95% CI: 0.98-5.40), while men carriers of I1(761)*CA(12) have decreased susceptibility (P = 0.022; OR: 0.46, 95% CI: 0.23-0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA(12) allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.
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