Abstract
Objective: To test the hypothesis that the identification of mutation in the carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is consistent with a possible role for mutations in CPE in the development of coronary atherosclerosis. Methods: The study subjects consisted of 1084 consecutive patients (812 males and 272 females) who will undergo coronary angiography. The severity of coronary atherosclerosis was defined by the Gensini’s score system. The proinsulin level was measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the 4th exon and exon-intron junctional region of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. Results: Sequencing of the CPE gene exon 4 in 1084 consecutive patients revealed 2 genetic variants, the G–to-A substitution at nucleotide 2855 in exon 4 (synonymous mutation) and A-to-G substitution at nucleotide 2925 in intron 4. Although the proinsulin level was not influenced by the presence of the two point mutation, the Gensini score was significantly influenced by the presence of the A2925G mutant (P = 0.023). Furthermore, we found a higher prevalence of subjects with the A2925G heterozygous mutant among higher Gensini score subjects than it among lower Gensini score subjects, and this difference reached statistical significance (P = 0.006, OR 1.465, 95%CI 1.116–1.924). In addition, the frequency distribution of the G2855A mutant was differed in the higher Gensini score subjects than it in the lower Gensini score subjects belonging to high-risk category as smokers, and the statistical significance was reached (P = 0.043, OR 2.075, 95%CI 1.024–4.207). Conclusions: In the present study, the severity of the coronary atherosclerosis estimated by Gensini score was significantly influenced by the presence of the A2925G mutant and G2855A mutant of the CPE gene, and the exactly mechanism underlying the association needs further study.
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Acknowledgements
Special thanks to Dr. Lennart Andersen, Dr. Jens Christian Wortmann, and Dr. Thomas Peter Dyrberg, at Novo Nordisk, Bagsvaerd, Denmark, for providing the free monoclonal antibodies including OXI-005, HUI-018, PEP-001 and HUI-001. This study was supported by the National Natural Science Foundation of China, No. 30400173 to Dr. Enzhi Jia.
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Jia, EZ., Wang, J., Yang, ZJ. et al. Association of the mutation for the human carboxypeptidase E gene exon 4 with the severity of coronary artery atherosclerosis. Mol Biol Rep 36, 245–254 (2009). https://doi.org/10.1007/s11033-007-9173-4
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DOI: https://doi.org/10.1007/s11033-007-9173-4