Correlations of lipoprotein(a) gene polymorphisms with calcific aortic valve disease and coronary heart disease
Dong Hongzhi1,2, Cong Hongliang2, Wang Jing3, Jiang Yiyao4,5, Liu Chao6, Zhang Yingyi2, Zhu Yanbo7, Wang Qingtong8
1Graduate School, Tianjin Medical University 300070, China; 2Department of Cardiology, Tianjin Chest Hospital, Tianjin 300051, China; 3Department of Pathology, Tianjin Chest Hospital, Tianjin 300051, China; 4Department of Cardiovascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; 5Department of Cardiovascular Surgery, the First Central Hospital Affiliated to Nankai University, Tianjin 300192, China; 6Institution of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin 300051, China; 7Department of Ultrasonography, Tianjin Chest Hospital, Tianjin 300051, China; 8Department of Clinical Laboratory, Tianjin Chest Hospital, Tianjin 300051, China
Abstract：Objective To investigate the relationships of lipoprotein(a) [Lp(a)] gene polymorphism with calcified aortic valve disease (CAVD) and coronary heart disease (CHD) .Methods Prospective study. A total of 248 patients with CHD or CAVD diagnosed in the Department of Cardiology of Tianjin Chest Hospital from January to December 2018 were divided into two groups, namely, the CAVD group (101 cases) and the CHD group (147 cases), in accordance with the results of color Doppler echocardiography, coronary angiography, and computed tomography angiography. The control group, which was composed of 171 cases who neither had CHD nor CAVD, was selected from the physical examination center from March to December 2018. Biomarkers, including Lp(a), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) were tested. The SNaPshot single nucleotide polymorphism method was used to detect Lp(a) gene loci rs10455872, rs6415084, and rs7770628. Binary logistic regression was performed to analyze the effects of different genotypes and Lp(a) levels on CAVD or CHD, and linear regression was conducted to analyze the effects of different genotypes and ApoB levels on Lp(a) levels.Results There were no statistically significant differences in BMI and drinking history among the three groups (all P values >0.05), and there were statistically significant differences in gender, age, smoking history, history of diabetes and hypertension (all P values <0.05). The Lp(a) quartile values of the control, CAVD, and CHD groups were 23.6 (9.4, 48.6), 37.2 (16.5, 79.6) , and 46.7 (21.5, 104.6) nmol/L, respectively, and exhibited a statistically significant difference (H=13.337, P<0.01). The LDL values of the control, CAVD, and CHD groups were(2.74±0.80), (3.07±0.81), and (3.14±1.18) mmol/L, respectively, and demonstrated a statistically significant difference (F=3.662, P<0.05). The HDL values of the control, CAVD, and CHD groups were (1.24±0.93), (1.18±0.30), and (1.09±0.33) mmol/L, respectively, and presented a statistically significant difference (F=4.281, P<0.05). The ApoA values of the control, CAVD, and CHD groups were 1.42±0.25, 1.30±0.26, and 1.26±0.26 g/L, respectively, and had a statistically significant difference (F=7.339, P<0.01). The ApoB quartile values of the control, CAVD, and CHD groups were 0.97 (0.82, 1.10), 1.04 (0.87, 1.26), and 1.12 (0.88, 1.31) g/L, respectively, and exhibited a statistically significant difference (H=3.948, P<0.05). The TT genotypes of the rs7770628 gene loci in the control, CAVD, and CHD groups were 130 (76.0%), 75 (74.3%), and 103(70.1%), respectively; the CT genotypes were 36 (21.1%), 23 (22.8%), and 40 (27.2%), respectively; the CC genotypes were 5 (2.9%), 3 (2.9%), and 4(2.7%), respectively; and no statistically significant difference was observed among the three groups (F=1.718, P>0.05). The TT genotypes of the rs6415084 gene loci in the control, CAVD, and CHD groups were 5 (2.9%), 2 (2.0%), and 4 (2.7%), respectively; the CT genotypes were 33 (19.3%), 20 (19.8%), and 32 (21.8%), respectively; the CC genotypes were 133 (77.8%), 79 (78.2%), and 111 (75.5%), respectively; and no statistically significant difference was noted among the three groups (F=0.551, P>0.05). The AA genotypes of the rs10455872 gene loci in the control, CAVD, and CHD groups were 171 (100%), 99 (98.0%), and 147 (100%), respectively; the AG genotypes were 0 (0.0%), 2 (2.0%), and 0 (0.0%), respectively; and no statistically significant difference was recorded among the three groups (P=0.058). The results of the logistic regression analysis showed that the Lp(a) level and the risks of CAVD and CHD increased compared with the control group. However, no statistically significant difference was found in the gene distribution frequency of the rs7770628 and rs6415084 gene loci between the CAVD and control groups. In addition, the difference in the gene distribution frequency between the CHD and control groups was not statistically significant (P>0.05). Linear regression indicated that the gene distribution of the rs7770628 and rs6415084 gene loci were related to the increase in Lp(a) concentration. The data of the rs10455872 gene loci disclosed that only two cases carried AG minor alleles among the 419 subjects, and both cases belong to the CAVD group. The remaining 417 cases carried AA minor alleles.Conclusions Lp(a) rs6415084 and rs7770628 genetic variations are associated with increased plasma Lp(a) level. High plasma Lp(a) levels are correlated with increased risk of CAVD and CHD.
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2020, Vol. 25 
