Abstract
BackgroundCytokines are known to be key players in dry eye syndrome (DES) and Sjogren’s syndrome (SS) pathogenesis. In this study we compared single nucleotide polymorphism (SNP) variations in genes encoding cytokine levels among SS and DES patients in Israel.MethodsWe recruited 180 subjects, 82 with SS and 98 with DES. Using a candidate gene approach and allele-specific PCR technique for genotyping, proportions of risk alleles in Tumor Necrosis Factor α (TNFα) (rs1800629), IinterLeukin-10 (IL-10) (rs1800896) and TNFAIP3 (rs2230926) SNPs were compared between study groups.ResultsAllelic distribution was found very similar to Caucasian (CEU – Utah residents with Northern and Western European roots) population distributions in these SNPs. While none of the SNPs’ variants were significantly associated with SS or DES in a recessive model, in an additive model the TNFα G risk allele was found higher among SS patients compared to DES (Homozygote-G: 84.2% vs. 70.8%; Heterozygote: 26.9% vs. 11.2%, respectively, p = 0.02). After adjustment for age, gender and ethnicity, these variants weren’t associated with SS. Genetic scoring reveals that SS patients are more likely to present variants of all three SNPs than DES subjects.ConclusionsThis is the first study evaluating these SNP variations among both patients with DES and patients with SS. We found the allelic distribution in each SNP to be very similar to that found in healthy Caucasian populations presented in the HapMap project. We found the TNFα allele significantly associated with DES for homozygotes, and associated with SS for heterozygotes in the additive model.
Highlights
Cytokines are known to be key players in dry eye syndrome (DES) and Sjogren’s syndrome (SS) pathogenesis
A genetic score (Table 4) was constructed by summing the prevalence of 1, 2 or 3 single nucleotide polymorphism (SNP)’ variations in each individual with SS or DES. These results show that more patients with DES carry 1 or 2 of the risk alleles of the tested SNPs than SS patients (58.3% vs 41.7 and 54.5% vs 45.5%, respectively), while variation in three SNPs was more common in SS than DES (58.3% vs 41.7), but the findings were not statistically significant (P = 0.60)
We found the allelic distribution in each SNP among patients with SS and DES very similar to that found in Caucasian populations (CEU) presented in the HapMap project, which validates our findings
Summary
Cytokines are known to be key players in dry eye syndrome (DES) and Sjogren’s syndrome (SS) pathogenesis. In this study we compared single nucleotide polymorphism (SNP) variations in genes encoding cytokine levels among SS and DES patients in Israel. SS is characterized mainly by severe dry eyes (xerophthalmia) and dry mouth (xerostomia), and can be primary (pSS) or secondary (sSS) to other AID [3, 4]. Both DES and SS are known to be associated with elevated cytokine levels in the serum, including. The gene TNFAIP3 (rs2230926G) (A20) was found to be highly associated with pSS progression [8, 18, 19]
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