ABSTRACT
OBJECTIVE: To investigate the association between the KCNE1 gene G38S and the KCNE4 gene E145D and atrial fibrillation in Uygur and Han populations living in Xinjiang. METHODS: KCNE1 gene G38S and the KCNE4 gene E145D genotype and frequency were determined using PCR restriction fragment length polymorphism (PCR-RFLP) in 488 atrial fibrillation patients (237 Uygur and 251 Han residents) and 488 age-and-gender matched controls (237 Uygur and 251 Han residents). RESULTS: Genotype and allele frequency of KCNE1 gene G38S were similar between atrial fibrillation group and control group in the Han population (P = 0.556, P = 0.946). In the Uygur population, there was a statistical difference between atrial fibrillation group and control group (P = 0.018, P = 0.003). Logistic regression analysis revealed the KCNE1 38 G was one of the independent risk factors for atrial fibrillation in the Uygur population (OR = 1.634, 95%CI: 1.192-2.240, P = 0.002). The KCNE4 gene E145D, genotype and allele frequency were significantly different between atrial fibrillation group and control group in the Uygur population and Han population (P = 0.041, P = 0.015;P = 0.032, P = 0.013) . Logistic regression analysis revealed the KCNE4 145D was one of the independent risk factors for atrial fibrillation in the Uygur population and Han population (OR = 1.636, 95%CI:1.173-2.281, P = 0.004; OR = 1.491, 95%CI:1.076-2.065, P = 0.016) . CONCLUSIONS: KCNE1 G38S is not associated with atrial fibrillation in the Han population while the KCNE1 G38S is associated with atrial fibrillation in the Uygur population. KCNE4 gene E145D is associated with atrial fibrillation in both Uygur population and Han population.
Subject(s)
Atrial Fibrillation/genetics , Polymorphism, Single Nucleotide , Potassium Channels, Voltage-Gated/genetics , Aged , Asian People/genetics , Atrial Fibrillation/ethnology , Case-Control Studies , China , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Risk FactorsABSTRACT
Action potential (AP) contours vary considerably between the fibers of normal adult and aged left atria. The underlying ionic and molecular mechanisms that mediate these differences remain unknown. The aim of the present study was to investigate whether the L-type calcium current (ICa.L) and the L-type Ca2+ channel of the left atria may be altered with age to contribute to atrial fibrillation (AF). Two groups of mongrel dogs (normal adults, 2-2.5 years old and older dogs, >8 years old) were used in this study. The inducibility of AF was quantitated using the cumulative window of vulnerability (WOV). A whole-cell patch-clamp was used to record APs and ICa.L in left atrial (LA) cells obtained from the two groups of dogs. Protein and mRNA expression levels of the a1C (Cav1.2) subunit of the L-type calcium channel were assessed using western blotting and quantitative PCR (qPCR), respectively. Although the resting potential, AP amplitude and did not differ with age, the plateau potential was more negative and the APD90 was longer in the aged cells compared with that in normal adult cells. Aged LA cells exhibited lower peak ICa.L current densities than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein expression levels in LA cells were decreased in the aged group compared with those in the normal adult group. The lower AP plateau potential and the decreased ICa.L of LA cells in aged dogs may contribute to the slow and discontinuous conduction of the left atria. Furthermore, the reduction of the expression levels of Cav1.2 with age may be the molecular mechanism that mediates the decline in ICa.L with increasing age.
