Tumor necrosis factor beta (TNF-β) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1.
This study evaluated the association of tumor necrosis factor beta (TNF-β) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-β genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-β NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.
Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil, anapaulakallaur@yahoo.com.br.
A P
AP
Kallaur
S R
SR
Oliveira
A N C
AN
Simão
E R D
ER
de Almeida
H K
HK
Morimoto
J
J
Lopes
L M
LM
Pelegrino
W L C J
WL
de Pereira
Daniele Frizon
DF
Alfieri
R M
RM
Andrade
S D
SD
Borelli
M A E
MA
Watanabe
D R
DR
Kaimen-Maciel
E M V
EM
Reiche
D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044465:White People
D059811:HLA-DRB1 Chains; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha