Background HIF-1α is the main transcriptional regulator of cellular and developmental response to hypoxia, and also participates in the integration of the T cell receptor and cytokine receptor-mediated signals of CD4+ helper cells. Another transcription factor also involved in the immune responses is the AT-hook transcription factor (AKNA).
Objectives To evaluate the allele and genotype frequencies of polymorphic sites of HIF1A and ANKA genes in primary Sjögren's syndrome (pSS).
Methods We included 110 patients with pSS and 141 ethnically matched healthy controls. Three HIF1A gene polymorphisms (Pro582Ser, Ala588Thr, and C191T) and two AKNA genes polymorphism (-1372C>A, and Pro624Leu) were genotyped using TaqMan probes in a Real-Time PCR instrument. Associations between pSS and genotypes, alleles and inheritance models of the SNPs of interest were evaluated by logistic regression adjusted by age and gender.
Results Most of the patients were females (95.4%), median age 55 years and median disease duration of 7.8 years. The C/T genotype and the T allele of the HIF1A Pro582Ser polymorphism protected against pSS (OR=0.22; 95% CI=0.09–0.52; P<0.01; and OR=0.26; 95% CI=0.12–0.58; P<0.01; respectively). Whereas under a recessive model adjusted by age and gender, the AKNA -1372C>A polymorphism A/A genotype was associated with an increased risk of pSS (OR=2.60; 95% CI=1.11–6.12; P=0.03). Parotid enlargement was associated with the HIF1A gene polymorphism (rs11549465), conferring protection for the C/T genotype vs. C/C (OR=0.22; 95% CI 0.05–0.90, P=0.03). The allele T of the same polymorphism was also associated with parotid enlargement (OR=0.24, 95% CI=0.65–0.95; P=0.04). We did not find any association with any other clinical or serological feature.
Conclusions We identified HIF1A Pro582Ser T allele and C/T genotype as well as AKNA -1372C>A polymorphism A/A genotype as genetic factors associated with pSS. Further studies in other populations are needed to validate our findings and to shed some light on their functional implications.
Palazon A, Goldrath A, Nizet V, Johnson R. HIF transcription factors, inflammation and immunity. Immunity 2014; 41:518–28.
Sims-Mourtada JC, Bruce S, McKeller MR, et al. The human AKNA gene expresses multiple transcripts and protein isoforms as a result of alternative promoter usage, splicing, and polyadenylation. DNA Cell Biol 2005;24:325–38.
Disclosure of Interest None declared
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