Association of HLA-DRB1, HLA-DQB1 Alleles, and TNF-α Promoter Polymorphisms with Multiple Sclerosis in the Cuban Population

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the central nervous system. It is known that the Major Histocompatibility Complex class II region produces the most potent effect on MS genetic susceptibility. In addition, the genetic polymorphism within the TNF locus has been involved in the pathogenesis of various autoimmune diseases. This study has the purpose of evaluating HLA-DRB1, HLADQB1 alleles and TNF promotor alpha gene polymorphism (SNP TNF- α -238 G/A; - 243G/A; -308 G/A; - 375 G/A, -856 C/T; -862 C/A) in a sample of Cuban MS patients. Disease-associated HLA susceptibility alleles were genotyped by the SSP-PCR method. The TNF- α genotypes were identified by sequencing. The association was found between HLA and MS, DRB1*15:01, DRB1*14:01, DQA*01:02 and DQB1*06:02 being susceptibility alleles. TNF-α-308 G (OR=1,6, P<0,01) and TNF- α -238 G (OR=2,0, P<0,01) alleles had higher frequency among MS patients than control subjects. The odds ratio was increased among HLADRB1*1501 positive individuals. Our results have shown that the combination of TNF-α-238 G, -308 G with HLA-DRB1*15:01 and HLA-DQA1*01:02 increased susceptibility to MS (p<0.05 OR=4.2) in the Cuban population. Keywords: HLA, TNF-Alpha, polymorphism, SNP, Multiple Sclerosis, Cuban population