Tumor necrosis factor-alpha microsatellite polymorphism association with rheumatoid arthritis in Indian patients.
BACKGROUND
Level of TNF-alpha increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population.


METHODS
In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity.


RESULTS
The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179, OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036, OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity.


CONCLUSIONS
In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA.
Agrawal
Charu
C
Institute of Genomics & Integrative Biology, Delhi University Campus, Delhi, India.
Raghav
Sunil Kumar
SK
Gupta
Bhawna
B
Das
Rakha Hari
RH
Chaturvedi
Ved Prakash
VP
Goswami
Kalyan
K
Das
Hasi Rani
HR
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha