HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population.
BACKGROUND
The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis.


OBJECTIVE
To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects.


METHODS
The SSP-PCR method was used to determine genotypes and Fisher's exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2-2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1-1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5-2.5, p < 0.0001).


RESULTS
Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501.


CONCLUSIONS
We suggest more studies to confirm these results in other populations.
Shahbazi
M
M
Medical Cellular and Molecular Research Center, Molecular Medicine and Genetics, Golestan University of Medical Sciences, Gorgan, Iran. Shahbazimajid@yahoo.co.uk
Ebadi
H
H
Fathi
D
D
Roshandel
D
D
Mohamadhosseni
M
M
Tahmasebi
A
A
Shahbazi
S
S
Zamani
M
M
Rashidbaghan
A
A
D000293:Adolescent; D000328:Adult; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D055815:Young Adult
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D015850:Interleukin-6; D019713:Receptors, CCR5; D004247:DNA