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Association evidence of CCTTT repeat polymorphism in the iNOS promoter and the risk of atrial fibrillation in Taiwanese

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ABSTRACT

Inducible nitric oxide synthase (iNOS) plays an important role in the pathogenesis of atrial fibrillation (AF). The iNOS promoter has a CCTTT-repeat length polymorphism that can determine the level of gene transcription. This study enrolled 200 AF patients and 240 controls. The length of CCTTT-repeat polymorphism in the iNOS promoter region was examined by polymerase chain reactions, with the alleles with ≤11 repeats designated as S and alleles with ≥12 repeats designated as L alleles. AF patients carried significantly higher frequencies of the LL genotype than control subjects (40.0% versus 28.3%, P = 0.010). Multivariate analysis showed that the presence of LL genotype was significantly associated with AF (odds ratio: 1.87, 95% CI = 1.10–3.17, P = 0.021). In vitro, transient transfection assay in HL-1 atrial myocytes showed that the responsiveness of iNOS transcriptional activity to tachypacing was correlated with the length of the CCTTT-repeats. Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients with LL genotype exhibited greater oxidative stress and substrate remodeling in their atria than those with non-LL genotypes. Our results suggest that the iNOS microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.

No MeSH data available.


Association of the CCTTT repeat length polymorphisms with myofibril degradation in AF tissues.Representative confocal images show myosin degradation in the atria of seven AF patients (4 non-LL and 3 LL) and two controls (with sinus rhythm [SR]). Relative intensity of MHC in the α-actin-expressing area was quantified as described in the Methods section. Data are expressed as mean ± SE. *P = 0.004, SR versus LL groups. #P = 0.004, non-LL versus LL groups. One-way ANOVA with post hoc Tukey’s tests was applied for two groups and multiple comparisons.
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f5: Association of the CCTTT repeat length polymorphisms with myofibril degradation in AF tissues.Representative confocal images show myosin degradation in the atria of seven AF patients (4 non-LL and 3 LL) and two controls (with sinus rhythm [SR]). Relative intensity of MHC in the α-actin-expressing area was quantified as described in the Methods section. Data are expressed as mean ± SE. *P = 0.004, SR versus LL groups. #P = 0.004, non-LL versus LL groups. One-way ANOVA with post hoc Tukey’s tests was applied for two groups and multiple comparisons.

Mentions: Our previous study showed that tachypacing promotes atrial structural remodeling, and especially myofibril degradation in atrial myocytes through increased oxidative stress25. To determine whether the CCTTT repeat polymorphisms affected AF-related oxidative stress and substrate remodeling, seven AF patients with four non-LL genotype and three LL genotype were chosen for comparison. Two sinus rhythm (SR) patients were designated as controls. The baseline characteristics of these nine patients are shown in the Table 3. We consistently found that oxidative stress (indicated by increased ROS generation, Fig. 4) and myofibril degradation (indicated by decreased myosin heavy chain (MHC) expression, Fig. 5) were more severe in the atria of the AF patients with LL genotype than in those with non-LL genotype and SR control. Taken together, these findings suggest that CCTTT repeat length polymorphisms may affect iNOS expression and consequent atrial structural remodeling responses in AF tissues.


Association evidence of CCTTT repeat polymorphism in the iNOS promoter and the risk of atrial fibrillation in Taiwanese
Association of the CCTTT repeat length polymorphisms with myofibril degradation in AF tissues.Representative confocal images show myosin degradation in the atria of seven AF patients (4 non-LL and 3 LL) and two controls (with sinus rhythm [SR]). Relative intensity of MHC in the α-actin-expressing area was quantified as described in the Methods section. Data are expressed as mean ± SE. *P = 0.004, SR versus LL groups. #P = 0.004, non-LL versus LL groups. One-way ANOVA with post hoc Tukey’s tests was applied for two groups and multiple comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304328&req=5

f5: Association of the CCTTT repeat length polymorphisms with myofibril degradation in AF tissues.Representative confocal images show myosin degradation in the atria of seven AF patients (4 non-LL and 3 LL) and two controls (with sinus rhythm [SR]). Relative intensity of MHC in the α-actin-expressing area was quantified as described in the Methods section. Data are expressed as mean ± SE. *P = 0.004, SR versus LL groups. #P = 0.004, non-LL versus LL groups. One-way ANOVA with post hoc Tukey’s tests was applied for two groups and multiple comparisons.
Mentions: Our previous study showed that tachypacing promotes atrial structural remodeling, and especially myofibril degradation in atrial myocytes through increased oxidative stress25. To determine whether the CCTTT repeat polymorphisms affected AF-related oxidative stress and substrate remodeling, seven AF patients with four non-LL genotype and three LL genotype were chosen for comparison. Two sinus rhythm (SR) patients were designated as controls. The baseline characteristics of these nine patients are shown in the Table 3. We consistently found that oxidative stress (indicated by increased ROS generation, Fig. 4) and myofibril degradation (indicated by decreased myosin heavy chain (MHC) expression, Fig. 5) were more severe in the atria of the AF patients with LL genotype than in those with non-LL genotype and SR control. Taken together, these findings suggest that CCTTT repeat length polymorphisms may affect iNOS expression and consequent atrial structural remodeling responses in AF tissues.

View Article: PubMed Central - PubMed

ABSTRACT

Inducible nitric oxide synthase (iNOS) plays an important role in the pathogenesis of atrial fibrillation (AF). The iNOS promoter has a CCTTT-repeat length polymorphism that can determine the level of gene transcription. This study enrolled 200 AF patients and 240 controls. The length of CCTTT-repeat polymorphism in the iNOS promoter region was examined by polymerase chain reactions, with the alleles with ≤11 repeats designated as S and alleles with ≥12 repeats designated as L alleles. AF patients carried significantly higher frequencies of the LL genotype than control subjects (40.0% versus 28.3%, P = 0.010). Multivariate analysis showed that the presence of LL genotype was significantly associated with AF (odds ratio: 1.87, 95% CI = 1.10–3.17, P = 0.021). In vitro, transient transfection assay in HL-1 atrial myocytes showed that the responsiveness of iNOS transcriptional activity to tachypacing was correlated with the length of the CCTTT-repeats. Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients with LL genotype exhibited greater oxidative stress and substrate remodeling in their atria than those with non-LL genotypes. Our results suggest that the iNOS microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.

No MeSH data available.