Abstract
Background: Our previous study found that the telomerase-associated protein 1 (TEP1, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (RECQL5, rs820196) single nucleotide polymorphisms (SNPs) were associated with changes in heart rate (HR) ≥ 30% during peritoneal lavage with distilled water after gastrectomy. This study established a single tube method for detecting these three SNPs using two-dimensional (2D) polymerase chain reaction (PCR), and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability (HRV). Aim: To investigate whether genotypes, genetic patterns, SNP-SNP and SNP-environment interactions were associated with HRV. Methods: 2D PCR was used to establish a single-tube method to detect TEP1 rs938886 and rs1713449 and RECQL5 rs820196, and the results were compared with those of sanger sequencing. After adjusting for confounders such as age, sex, smoking, hypertension, and thyroid dysfunction, a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns (codominant, dominant, overdominant, recessive, and additive) of the three SNPs and a risk ≥ 15% or ≥ 30% of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer. Gene-gene and gene-environment interactions were analyzed using generalized multifactor dimensionality reduction. Results: The coincidence rate between the 2D PCR and sequencing was 100%. When the HRV cutoff value was 15%, the patients with the RECQL5 (rs820196) TC genotype had a higher risk of high HRV than those who had the TT genotype (odds ratio = 1.97; 95%CI: 1.05-3.70; P = 0.045). Under the codominant and overdominant models, the TC genotype of RECQL5 (rs820196) was associated with a higher risk of HR decrease relative to the TT and TT + CC genotypes (P = 0.031 and 0.016, respectively). When the HRV cutoff value was 30%, patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG-TT genotype carriers (P = 0.01). In the three-factor model of rs938886, rs820196, and rs1713449, patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers (P = 0.01). For rs820196, nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.04). When the HRV cutoff value was 15%, patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers (P = 0.04 and 0.01, respectively). Patients carrying the GC-CT-TC genotypes of rs938886, rs1713449, and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers (P = 0.02). When the HRV cutoff value was 15%, the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking (P = 0.022) and rs820196-hypertension (P = 0.043) models. Consistent with the results of the previous grouping, for rs820196, the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype (P = 0.01). Conclusion: The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.