Association of genetic polymorphisms on BTNL2 with susceptibility to and prognosis of dilated cardiomyopathy in a Chinese population.

BACKGROUND Dilated cardiomyopathy (DCM) is one type of primary myocardial disease, partly caused by immunity dysfunctions. BTNL2 (butyrophilin-like 2) has already been confirmed to be involved in the etiology of autoimmune disorders and GWAS (genome wide association study) has also identified mutants of a SNP (single nucleotide polymorphism) near BTNL2 could modulate risk of coronary heart disease (also cardiomyopathy). The current study, therefore, was aimed to investigate whether polymorphisms within or around BTNL2 would be correlated with susceptibility to and prognosis of DCM. MATERIAL AND METHODS Peripheral blood samples were gathered from 82 DCM patients and 75 healthy controls. Nine tag-SNPs within or near BTNL2 were obtained from HapMap Database and previously published studies. Eligible haplotypes were gained on the basis of SHesis software. Genotyping of SNPs was implemented with aid of Sequenom MassArray iPLEX platform and subsequently analyzed via MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were utilized to evaluate the correlations between SNPs/haplotypes and DCM risks. Finally, Cox proportional hazard models and Kaplan-Meier curves were performed to assess association of SNPs/haplotypes with prognosis of DCM patients. The statistical analyses were conducted with SPSS 19.0 software. RESULTS Under the allelic model, rs3763313 (A > C), rs9268494 (C > A), rs9268492 (C > G) and rs9268402 (A > G) were remarkably associated with susceptibility to grade IV of DCM classified by NYHA (New York heart association) (OR = 0.43, 95% CI: 0.22-0.84; P = 0.018; OR = 0.49, 95% CI: 0.27-0.91; P = 0.024; OR = 0.50, 95% CI: 0.27-0.94; P = 0.035; OR = 0.53, 95% CI: 0.28-0.97; P = 0.048). Haplotype C-C-A-T (rs9268492, rs9268494, rs3763313 and rs3763317 synthesized) was also regarded as a protective factor for DCM patients compared with carriers of other haplotypes (OR = 0.50, 95% CI: 0.26-0.97, P = 0.038). Moreover, the univariate survival analysis and multivariate Cox regression analysis both indicated noticeable correlations between rs9268402 and haplotype C-C-A-T and prognosis of DCM patients (NYHA IV), respectively (Long-Rank P = 0.029, HR: 0.241, 95% CI: 0.089-0.650, P = 0.005; Long-Rank P = 0.036; HR = 0.126, 95% CI: 0.035-0.457, P = 0.002). Nonetheless, rs3763313 was found only associated with prognosis of DCM patients (NYHA IV) expressed in the Kaplan-Meier curve (P = 0.009). CONCLUSION The genetic mutations within or around BTNL2 (rs3763313, rs9268494, rs9268492 and rs9268402) could alter susceptibility to grade IV of DCM in a Chinese population, and the 2 SNPs (rs3763313 and rs9268402) therein added with haplotype C-C-A-T might separately predict the prognosis of DCM patients. However, additional studies regarding diverse ethnicities need to be furthered to validate our results.