Association between C1019T polymorphism of the connexin37 gene and coronary heart disease in patients with in-stent restenosis

Abstract

Studies have shown that a C1019T polymorphism of the gene encoding the gap junction protein connexin37 is associated with coronary artery disease (CAD). The aim of the present study was to explore the association between the C1019T polymorphism in the connexin37 gene and CAD patients with in-stent restenosis (ISR). A total of 532 patients who had undergone coronary stenting and coronary angiography at least three months after the procedure were divided according to a clinical diagnosis standard into two groups which were ISR (n=67) and no in-stent restenosis (NISR; n=465) groups. A further 501 healthy individuals were controls. The subjects were genotyped by DNA sequencing. The results demonstrated the following: i) connexin37 gene 1019 sites in the population were distributed by polymorphism into three genetic types (CC, TC and TT types). The distribution frequency of the healthy control, ISR and NISR groups conformed to the Hardy-Weinberg genetic balance rule; ii) in comparison with the healthy controls, the frequency of the connexin37 C allele was higher in the CAD patients (57.05% vs. 41.32%; OR, 1.89; 95% CI, 1.58–2.25; P<0.01). The frequency of the C carriers (CC+TC) was 65.47% in the healthy controls, vs. 79.32% in CAD patients (P<0.01). The CAD risk was significantly increased in the carriers of the C allele (CC+TC) compared with TT homozygotes (OR, 2.03; 95% CI, 1.53–2.80; P<0.01). Stratified analysis demonstrated that a significant difference existed in the frequency of C carriers between the male CAD patients and healthy controls (79.63% vs. 72.45%; OR, 1.48; 95% CI, 1.06–2.09, P=0.02), as well as in the female CAD patients (78.00% vs. 51.50%; OR, 3.34; 95% CI, 1.90–5.86; P<0.01). In the female and male CAD patients, the frequency of the connexin37 C allele was higher than in the healthy controls (male: χ2=12.67, P<0.01; female: χ2=50.20, P<0.01); iii) compared with the NISR group, the frequencies of the connexin37 C allele and C carriers (CC+TC) were significantly higher in the ISR group (frequency of C allele: 72.39% vs. 54.84%; P<0.01; frequency of C carriers: 89.55% vs. 77.85%; P=0.03). Compared with TT homozygotes, the restenosis risk was significantly increased in the carriers of the C allele (CC+TC; OR, 2.44; 95% CI, 1.08–5.50). Subsequent stratified analysis revealed that the frequency of the C allele was significantly higher in the male ISR group than in the male NISR group (78.57% vs. 52.66%; OR, 3.30; 95% CI, 2.05–5.29; P<0.01). The restenosis risk was ∼four-fold higher in the C carriers (CC+TC) than in the TT homozygotes (OR, 3.74; 95% CI, 1.32–10.64). However in the female population, there was no difference in the ISR risk between the carriers of the C allele (CC+TC) and the TT homozygotes (P=0.70). In summary, the C allele of the connexin37 gene is not only is associated with the susceptibility to CAD, but also associated with restenosis following coronary stenting in the population studied herein, particularly the male population.