Single nucleotide polymorphism in CPT1B and CPT2 genes and its association with blood carnitine levels in acute myocardial infarction patients |
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Authors: | Haseeb Ahmad Khan Abdullah Saleh Alhomida |
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Affiliation: | Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia |
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Abstract: | Ischemic and reperfusion injuries in acute myocardial infarction (AMI) lead to mitochondrial dysfunction in heart cells. Lipid metabolism takes place in mitochondria where carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into matrix to provide substrates for beta-oxidation. We sequenced the coding regions of CPT1B and CPT2 genes to identify the single nucleotide polymorphism (SNP) in 23 AMI patients and 23 normal subjects. We also determined blood carnitine levels in these samples to study the impact of these SNPs on carnitine homeostasis. The sequencing of coding regions revealed 4 novel variants in CPT1B gene (G320D, S427C, E531K, and A627E) and 2 variants in CPT2 gene (V368I and M647V). There were significant increases in total carnitine (54.18 ± 3.11 versus 21.49 ± 1.03 μmol/l) and free carnitine (37.78 ± 1.87 versus 10.06 ± 0.80 μmol/l) levels in AMI patients as compared to normal subjects. CPT1B heterozygous variants of G320D and S427C among control subjects showed significantly higher levels of total and free carnitine in the blood. The homozygous genotype (AA) of CPT2 variant V368I had significantly less blood carnitine in AMI patients. Serum troponin T was significantly less in GG genotype of CPT1B variant S427C whereas the genotype AA of CPT2 variant V368I showed significantly higher serum troponin T levels. Further studies on large number of patients are necessary to confirm the role of CPT1B and CPT2 polymorphism in AMI. |
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Keywords: | AMI, acute myocardial infarction BMI, body mass index CAD, coronary artery disease CoA, coenzyme A CPT1B, carnitine palmitoyltransferase IB CPT2, carnitine palmitoyltransferase II dbSNP, database of single nucleotide polymorphism DNA, deoxyribonucleic acid dNTP, deoxyribonucleotides ELISA, enzyme-linked immunosorbent assay LC-MS/MS, liquid chromatography-tandem mass spectrometry NSTEMI, non-ST-elevated myocardial infarction PCR, polymerase chain reaction SNP, single nucleotide polymorphism STEMI, ST-elevated myocardial infarction |
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