Association of T66A polymorphism in CASQ2 with PR interval in a Chinese population

The aim of this study was to explore the relationship between arrhythmia-associated or electrocardiogram (ECG)-associated common variants and PR interval, QRS duration, QT_corrected, and heart rate in a Chinese cohort.

We studied the association between 26 single-nucleotide polymorphisms (SNPs) and digital ECG data from 379 unrelated Han Chinese individuals collected in an epidemiological survey in Beijing. All subjects were 45 years of age or older and were free of cardiovascular diseases and diabetes. The SNPs were genotyped in a multiplex panel using the Sequenom MassARRAY platform.

Missense variant T66A (Thr66Ala, rs4074536) of the CASQ2 gene, which was previously reported to be associated with QRS complex in European populations, was significantly associated with PR interval prolongation in our sample (p_adjusted = 0.006, beta_adjusted = 3.983 ms). A two-tailed t test showed that the CC genotype (n = 86) had a significantly longer PR interval (162.9 ± 19.4 ms) than the non-CC genotypes (n = 288, PR interval: 154.6 ± 20.9 ms), with a remarkable difference of 8.2 ms between the groups (p = 0.001). Interestingly, this association between T66A of CASQ2 and PR interval was more evident in females (p_adjusted = 0.007, beta_adjusted = 5.723 ms) than in males (p_adjusted = 0.177, beta_adjusted = 2.725 ms). In addition, rs3822714 in the HAND1 locus might be associated with QRS duration (p_adjusted = 0.034, beta_adjusted = -2.268 ms).

We identified a novel signal of an association between the CC genotype of T66A in CASQ2 and PR interval prolongation in a Chinese population, particularly in females. This association deserves further exploration given its possible effects on calcium handling in cardiac electrophysiology.