Objective: Atrial fibrosis plays a key role in the inducibility and persistence of atrial fibrillation. Urotensin II (U-II/UTS2) induces cardiac fibrosis by increasing fibroblast collagen synthesis and increased U-II plasma levels have been reported in patients with atrial fibrosis. Our objective was therefore to evaluate the possible role of the UTS2 gene polymorphisms Thr21Met and Ser89Asn in the genetic susceptibility to atrial fibrillation in a Chinese population.
Methods: A case-control study was designed to compare the distribution of alleles and genotypes between controls (n=197) and patients with AF (n=197). The detection of UTS2 gene polymorphisms was undertaken using the PCR-restriction fragment length polymorphism technique.
Results: We identified statistically significant differences between the atrial fibrillation and control groups with regard to the frequency of genotype variant GA at the Ser89Asn locus (OR 1.955, 95% CI 1.071 to 3.566, p=0.029). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn was only seen in men in the additive tested inheritance model (OR 2.843, 95% CI 1.273 to 6.348, p=0.011). There was a statistical difference in Met21Met, implying a potential beneficial role for atrial fibrillation in the recessive tested inheritance model among men (OR 0.260, 95% CI 0.075 to 0.89, p=0.033; AA vs GA-GG). For subjects with atrial fibrillation, the Met21Met genotype was associated with a larger anteroposterior left atrial diameter (AA vs GG, 4.12±0.62 vs 3.86±0.51, p=0.028) and a smaller left ventricular end-diastolic diameter (AA vs GG, 4.50±0.48 vs 4.78±0.49, p=0.039).
Conclusions: Ser89Asn polymorphisms of the UTS2 gene are significantly associated with atrial fibrillation in the Chinese population. Additionally, we demonstrated that genotype Met21Met may have a potential beneficial role in atrial fibrillation.
Keywords: Urotensin-II; atrial fibrillation; single nucleotide polymorphisms.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/