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The percentage of males was significantly higher among young CHD patients than older CHD patients (P = 0.0025). The differences in BMI (P = 0.130), CK (P = 0.180), cTnT (P = 0.453), BNP (P = 0.705), TC (P = 0.023), TG (P= 0.569), Fib (P = 0.135), hs-CRP (P = 0.257), LDL-C (P = 0.541), blood glucose (P = 0.757), HDL-C (P = 0.190), and DD (P = 0.267) between the case and experimental groups were not significant (Table 1). There are no significant differences among BMI, TC, TG, Fib, hs-CRP, LDL-C, blood glucose, HDL-C, and DD except CK, cTNT and BNP, which stand for myocardial damage.
Items Case Group (Young CHD) Experimental Group (Older CHD) Control Group (Non-CHD) P1 P2 P3 115 100 100 Gender (male) 110 (96%) 73 (73%) 50 (50%) 0.0025* 0.001* 0.722 Age (y) 37 ± 8 69 ± 19 45 ± 25 0.005* 0.072 0.065 BMI (kg/m2) 27.260 ± 4.429 26.441 ± 4.003 25.123 ± 2.987 0.130 0.250 0.654 CK (U/L) 412.250 ± 932.448 116.263 ± 228.850 45.235 ± 37.336 0.180 0.001* 0.001* cTnT (ng/mL) 1.432 ± 4.801 1.518 ± 0.051 0.002 ± 0.005 0.453 0.001* 0.001* BNP (pg/mL) 430.061 ± 1100.702 657.453 ± 481.990 145.859 ± 170.33 0.705 0.051 0.062 TC (mmol/L) 4.451 ± 1.354 4.038 ± 0.943 4.208 ± 0.552 0.053 0.223 0.365 TG (mmol/L) 2.133 ± 1.762 1.978 ± 1.353 1.523 ± 1.044 0.569 0.078 0.061 Fib (g/L) 3.136 ± 0.837 3.108 ± 0.749 2.744 ± 0.965 0.135 0.123 0.115 hs-CRP (mg/dL) 0.543 ± 0.852 0.619 ± 1.629 0.212 ± 0.158 0.257 0.075 0.062 LDL-C (mg/dL) 2.774 ± 1.104 2.672 ± 0.761 1.511 ± 0.526 0.541 0.056 0.051 blood glucose (mmol/L) 6.466 ± 1.728 5.907 ± 1.104 4.859 ± 1.158 0.190 0.093 0.125 HDL-C (mmol/L) 0.966 ± 0.254 0.989 ± 0.271 1.025 ± 0.056 0.757 0.799 0.852 D-dimer (µg/mL) 0.355 ± 0.542 0.401 ± 0.683 0.258 ± 0.026 0.467 0.087 0.056 Note.BMI: body mass index, CK: creatine kinase, cTnT: cardiac troponin t, BNP: brain natriuretic peptide, TC: total cholesterol, TG: triglyceride, Fib: fibrinogen, hs-CRP: high-sensitivity C-reactive protein, LDL-C: low-density lipoprotein cholesterol, HDL-C: high-density lipoprotein cholesterol. Independent sample t test. ANOVA method, P < 0.05 represent significantly different. P1 stands for the comparison between Case group and Experimental group, P2 stands for the comparison between Case group and Control group, P3 stands for the comparison between Experimental group and Control group. *P < 0.05. Table 1. Comparison of the Blood Biochemical Indicators between the Groups
Two young CHD patients with the mitochondrial C5263T single-nucleotide mutation underwent coronary angiography. Patient A carrying the mitochondrial C5263T single nucleotide mutation had 100% stenosis at the single nucleotide mutation had 100% stenosis at the proximal end of the circumflex branch (Figure 1B). Proximal end of the anterior descending branch (Figure 1A), and Patient B carrying the mitochondrial C5263T.
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Mitochondrial gene full sequence scanning of all patients and comparison with the 2013 edition of the Revised Cambridge Reference Sequence resulted in the detection of a series of gene point mutations. All mitochondrial mutation results were compared with reported mitochondrial mutations [comparison source: MitoMap (http://www.mitomap.org)]. A total of 165 types of point mutations were discovered. Two young CHD patients had the C5263T single-nucleotide mutation in the ND2 gene (Figures 2 and 3). This mutation is highly evolutionarily conserved among higher animals such as humans and gorillas and was not detected in the experimental group. The mitochondrial gene full sequence scanning results of these 2 patients (Table 2) revealed that the HV2 gene had 2 mutation sites, the OHR gene had 1 mutation site, the HV3 gene had 1 mutation site, the RNR1 gene had 2 mutation sites, and the RNR2 gene had 2 mutation sites. Among the mutation sites, 24 were located in protein coding regions. However, with the exception of C5263T, the mutation sites exhibited poor conservation and have not been associated with CHD in the literature.
Gene Mutation Site Base Change Amino Acid Change Conservationa Reported Previouslybc Number 1 Number 2 HV2 A73G A-G Y 1 - G94A G-A Y 1 - OHR A263G A-G Y 1 1 HV3 T489C T-C Y 1 - RNR1 A750G A-G Y 1 1 A1438G A-G Y 1 1 RNR2 A2706G A-G Y 1 1 G3010A G-A Y 1 - T3109 deletion T-DEL Y 1 - ND1 G3316A G-A syn Y 1 - A3837T A-T syn Y - 1 C3970T C-T syn Y - 1 ND2 A4769G A-G syn Y 1 1 C4883T C-T syn Y 1 - C5178A C-A L-M L/S/T/T/S Y 1 - C5263T C-T A-V A/A/I/L/L Y 1 1 CO1 T5963C T-C syn Y 1 - T6392C T-C syn Y - 1 C7028T C-T syn Y 1 1 T7741C T-C syn Y - 1 G8020A G-A syn Y - 1 ATP6 C8575T C-T syn Y 1 A8701G A-G T-A T/S/L/L/Q Y 1 A8860G A-G T-A T/A/A/A/T Y 1 CO3 C9536T C-T syn Y 1 T9540C T-C syn Y 1 C9764T C-T syn Y 1 ND3 G10310A G-A syn Y 1 A10398G A-G T-S T/A/A/A/A Y 1 C10400T C-T syn Y 1 T10873C T-C syn Y 1 ND4 C11215T C-T syn Y 1 G11719A G-A syn Y 1 1 G11914A G-A syn Y 1 Note. aConservation of amino acid for polypeptides or nucleotide for rRNAs in humans (H), gorillas (O), mice (M), chickens (C), and zebrafish, (Z); bCambridge Reference Sequence; con-line mitochondrial gene database. Table 2. Analysis of the Full Sequence Scanning of Patients Carrying the Mitochondrial C5263T Mutation
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Among the probands in the 3-generation pedigree of Patient A carrying the C5263T point mutation (Figure 4A, made by Photoshop CS6), Ⅱ1 and Ⅱ3 both died of acute coronary syndrome. Among the probands in the 3-generation pedigree of Patient B carrying the C5263T point mutation (Figure 4B, made by Photoshop CS6), Ⅰ1 died of acute coronary syndrome, and Ⅱ3 did not participate in this study for personal reasons. Members in the third generation of these two family lineages did not yet have coronary artery disease due to their young ages. The penetrance rates of maternal members in the above family lineages were 100% and 75%, respectively. The maternal inheritance pattern suggests that the mitochondrial C5263T point mutation might participate in the occurrence and development of CHD among young people in these two 3-generation family lineages.
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The detection results were listed in The ROS level was significantly higher in the cells from the mutation group than the non-mutation group (4750.82 ± 1045.55 vs. 3888.58 ± 487.60, P = 0.022) (Table 3). The ratio between the JC-1 monomers and multimers was expressed in the form of P2/P3, which was inversely proportional to the MMP. The MMP in the mutation group was significantly lower than the MMP in the non-mutation group (0.77 ± 0.57 vs. 0.35 ± 0.14, P = 0.045).
Group Mutation Group Non-mutation t P ROS levels (U/well) 4750.82 ± 1045.55 3888.58 ± 487.60 2.301 0.022* Δψ 0.77 ± 0.57 0.35 ± 0.14 2.043 0.045* P 0.045* 0.386 Note. P value stands for the results of the comparison between mutation group and non-mutation group in ROS and MMP. *P < 0.05 represent significantly different. ROS: reactive oxygen species. Δψ: mitochondrial membrane potential. Table 3. ROS Levels and MMP in the Cells from the Mutation and non-mutation Group