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Immunol Lett. 2013 Feb;150(1-2):130-3. doi: 10.1016/j.imlet.2013.01.002. Epub 2013 Jan 11.

Genetic evidence for the involvement of NOTCH4 in rheumatoid arthritis and alopecia areata.

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Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait.


To explore the genetic association of single nucleotide polymorphisms (SNPs) in the coding region of the NOTCH4, exon 3 C+1297T and exon 5 A+3063G, in a case-control analysis of 58 rheumatoid arthritis (RA) and 98 alopecia areata (AA) and 100 ethnically matched healthy subjects. NOTCH4 polymorphisms were genotyped by standard PCR followed by restriction digestion. Analysis of C+1297T SNP revealed a significant association of allele C+1297 (p=0.03, OR=1.66, 95%CI 1.04-2.64) and genotype CT (p=0.002, OR=2.82, 95%CI 1.42-5.59) with susceptibility to RA. Analysis of A+3063G SNP revealed a significant association of allele A+3063 (p=0.05, OR=0.59, 95%CI 0.35-1.008) and genotype AA (p=0.002, OR=0.39, 95%CI 0.17-0.87) with RA. Over all analysis between alopecia patients and the studied SNPs failed to show any significant association. Classifying the patients by severity of disease, confined the risk role of CT genotype to the severest form of alopecia universalis (p=0.006, OR=3.82, 95%CI 1.39-3.82) and AG genotype to semiuniversalis alopecia (p=0.004, OR=4.3, 95%CI 1.5-15.3). Present study is the first to report a statistically significant association between RA and NOTCH4 polymorphisms.

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