TNF-α Genetic Polymorphisms and its Expression in Egyptian Rheumatoid Arthritis Patients

Abstract

Rheumatoid arthritis (RA) is a complex, multifactorial, inflammatory disease that affects more than 1.5 million adults. The current study aimed to investigate whether there is an association between either -376 G/A or -238 G/A polymorphisms of TNF-α promoter and the risk of RA in Egyptian patients, and investigate whether these polymorphisms are linked to TNF-α expression. DNA from 54 clinically confirmed RA patients and 24 apparently healthy individuals was genotyped by RFLP technique. Some samples were selected for semi-quantitative measurement of TNF-α mRNA expression. For the -376 polymorphism, no polymorphism was recorded in this site neither in RA patients nor in the apparently healthy individuals. This indicated the wide distribution of the wild type GG genotype among Egyptians. For the -238 G/A polymorphism, data indicated that 77.8% of RA patients were of the genotype GG and 22.2% were heterozygous (GA), while 91.7% of the apparently healthy individuals were of the genotype GG and 8.3% were heterozygous (GA). The homozygous genotype AA was not recorded in any RA or healthy subject. There was no statistically significant difference in the genotype distribution between RA patients and the apparently healthy individuals. Also, there was no statistically significant difference in either the G or A allele distribution between the RA group and the group of healthy subjects. Semi-quantitative PCR on some samples revealed a statistically significant increase in the relative expression of TNF-α mRNA in RA patients compared to healthy subjects. Based on these data, we conclude that -238 G/A and -376 G/A polymorphisms can not be considered as risk factors for RA among Egyptians and the increased expression of TNF-α in Egyptian RA patients is not linked to these polymorphisms. Therefore, Egyptian RA patients may have different genetic or environmental factors contributing to the pathogenesis of RA and further studies are necessary to search for other genetic polymorphisms and/or genes that contribute to the increased expression of TNF-α and hence the pathogenesis of RA in Egyptian patients.