Missense Variant rs28362680 in BTNL2 Reduces Risk of Coronary Heart Disease

Abstract

Jian Zhuo,1 Yingchun Wu,2 Wei Li,1 Zerong Li,1 Yipeng Ding,3 Tianbo Jin4,5 1Department of Emergency Service, People’s Hospital of Wanning, Wanning, Hainan, 571500, People’s Republic of China; 2Department of Intensive Care Unit, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, People’s Republic of China; 3Department of General Practice, Hainan General Hospital, Hainan affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, People’s Republic of China; 4Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi‘an, Shaanxi, 710069, People’s Republic of China; 5Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yipeng Ding, Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xinhua Road, Xiuying District, Haikou, 570311, Hainan, People’s Republic of China, Tel [phone], Email [email protected] Tianbo Jin, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, #229 Taibai North Road, Xi’an, 710069, Shaanxi, People’s Republic of China, Tel/Fax [phone], Email [email protected]: The pathological basis of coronary heart disease (CHD) is atherosclerosis. BTNL2 can inhibit the activation of T cells. We aimed to explore the association between BTNL2 genetic variants and CHD risk in the southern Chinese Han population.Methods: We recruited 1419 participants to perform an association analysis between missense variants in BTNL2 and CHD risk through SNPStats online software. Genotyping of all candidate SNPs were completed by the Agena MassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CHD risk was evaluated by multi-factor dimensionality reduction (MDR).Results: The results showed that BTNL2-rs35624343, -rs117896888, -rs41441651, -rs41417449, -rs28362680 and -rs2076523 were significantly associated with the CHD susceptibility. Especially for BTNL2-rs28362680, the allele A (OR = 0.68, p < 0.0001), genotype AA (OR = 0.40, p = 0.001) or GA (OR = 0.68, p < 0.0001) were associated with the reducing CHD risk. And -rs28362680 significantly reduced the CHD risk under all genetic models (dominant: OR = 0.64, p < 0.0001; recessive: OR = 0.47, p = 0.003; overdominant: OR = 0.73, p = 0.004; log-additive: OR = 0.66, p < 0.0001). And -rs28362680 was also closely associated with CHD risk reduction in all stratified analyses (age, gender, smoking, drinking, hypertension and diabetes). In addition, haplotype analysis showed that the “Crs117896888Crs41441651Trs41417449Ars28362680” (OR = 0.65, p < 0.0001) and “Grs117896888Trs41441651Crs41417449Ars28362680” (OR = 0.68, p = 0.013) may reduce CHD risk.Conclusion: Missense variants (rs35624343, rs117896888, rs41441651, rs41417449, rs28362680, rs2076523) may be protective factors for the CHD risk. In particular, there were sufficient evidences that BTNL2-rs28362680 can protective CHD risk.Keywords: coronary heart disease, BTNL2, missense variants, southern Chinese Han population

Keywords

• coronary heart disease
• btnl2
• missense variants
• southern chinese han population