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 heart disease. METHODS: The study subjects consisted of 51 consecutive patients (34 males and 17 females) who will undergo coronary angiography for suspected or known coronary atherosclerosis. Coronary heart disease (CHD) was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography or based on the Rose Questionnaire. The insulin and proinsulin level were measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the eight exons of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. RESULTS: We scanned eight exons and exon-intron junctional region. Overall, we found 12 distinct variants in the intron region and three variants in the exon region. Among the 15 variants, 10 mutations were rare. The further explored study reveal that the above five non-rare variants would not affect the level of glucose, insulin, and proinsulin. However, the results suggest that the prevalence of the coronary heart disease was significant difference between the wild type group and mutant type group according to the A4545G (P = 0.020). The results from the logistic regression reveal that the subjects with the CPE mutation of A4545G, the odds ratio for the coronary heart disease was 0.196 (95% CI: 0.046 to 0.830, P = 0.027). CONCLUSIONS: In the present study, the mutation of CPE gene would not affect the level of glucose, insulin, and proinsulin. The hypothesis of a possible role for mutations in CPE in the development of coronary heart disease needs further study.
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 heart disease. METHODS: The study subjects consisted of 51 consecutive patients (34 males and 17 females) who will undergo coronary angiography for suspected or known coronary atherosclerosis. Coronary heart disease (CHD) was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography or based on the Rose Questionnaire. The insulin and proinsulin level were measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the eight exons of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. RESULTS: We scanned eight exons and exon-intron junctional region. Overall, we found 12 distinct variants in the intron region and three variants in the exon region. Among the 15 variants, 10 mutations were rare. The further explored study reveal that the above five non-rare variants would not affect the level of glucose, insulin, and proinsulin. However, the results suggest that the prevalence of the coronary heart disease was significant difference between the wild type group and mutant type group according to the A4545G (P = 0.020). The results from the logistic regression reveal that the subjects with the CPE mutation of A4545G, the odds ratio for the coronary heart disease was 0.196 (95% CI: 0.046 to 0.830, P = 0.027). CONCLUSIONS: In the present study, the mutation of CPE gene would not affect the level of glucose, insulin, and proinsulin. The hypothesis of a possible role for mutations in CPE in the development of coronary heart disease needs further study.
Authors: H Chen; S Jawahar; Y Qian; Q Duong; G Chan; A Parker; J M Meyer; K J Moore; S Chayen; D J Gross; B Glaser; M A Permutt; L D Fricker Journal: Hum Mutat Date: 2001-08 Impact factor: 4.878
Authors: J K Naggert; L D Fricker; O Varlamov; P M Nishina; Y Rouille; D F Steiner; R J Carroll; B J Paigen; E H Leiter Journal: Nat Genet Date: 1995-06 Impact factor: 38.330
Authors: Niamh X Cawley; William C Wetsel; Saravana R K Murthy; Joshua J Park; Karel Pacak; Y Peng Loh Journal: Endocr Rev Date: 2012-03-07 Impact factor: 19.871
Authors: Ellen M Wijsman; Joseph H Rothstein; Robert P Igo; John D Brunzell; Arno G Motulsky; Gail P Jarvik Journal: Hum Genet Date: 2010-04-11 Impact factor: 4.132