title: Association of the mutation for the human carboxypeptidase E gene exon 4 with the severity of coronary artery atherosclerosis.
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.
authors: Department of Cardiovascular Medicine, the first affiliated hospital of Nanjing Medical University, Guangzhou road 300, Nanjing 210029, Jiangsu Province, China. enzhijia@yahoo.com.cn
authors: En-Zhi
authors: EZ
authors: Jia
authors: Jie
authors: J
authors: Wang
authors: Zhi-Jian
authors: ZJ
authors: Yang
authors: Tie-Bing
authors: TB
authors: Zhu
authors: Lian-Sheng
authors: LS
authors: Wang
authors: Hui
authors: H
authors: Wang
authors: Chun-Jian
authors: CJ
authors: Li
authors: Bo
authors: B
authors: Chen
authors: Ke-Jiang
authors: KJ
authors: Cao
authors: Jun
authors: J
authors: Huang
authors: Wen-Zhu
authors: WZ
authors: Ma
mesh_terms: D001483:Base Sequence; D043423:Carboxypeptidase H / Q000235:genetics*; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D019683:Penetrance; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: D043423:Carboxypeptidase H