title: Genetic variability of the distal promoter of the ST2 gene is associated with angiographic severity of coronary artery disease.
abstract: Genetic polymorphy of the distal promoter region of the ST2 gene influences transcriptional activity and susceptibility to atopic dermatitis and asthma. Based on the inflammatory background of atherosclerosis we hypothesized that ST2 distal promoter genetic polymorphy could also affect susceptibility to coronary artery disease (CAD). To test our hypothesis we performed direct sequencing of a 825 bp locus of the distal promoter -with previously reported significant polymorphy in 63 angiographically diagnosed CAD patients and 63 age and sex matched controls with negative coronary angiography. We identified 13 polymorphisms spanning this region two of which (-27307 T/A and -27614 C/A) had allele frequencies greater than 0.05. We further genotyped 111 subjects by applying allele-specific real-time PCR for the -27307 T/A and 27614 C/A polymorphisms, thereby increasing our sample to 129 CAD patients and 108 age- and sex-matched controls. We identified no phenotype-genotype interactions between cases and controls. However, among case subjects the severity of CAD expressed as a mean number of diseased vessels was greater in -27307 A allele carriers and either allele carriers (-27614 A or -27307 A) than in non-carriers (2.56 ± 0.73 vs. 1.83 ± 0.84, adjusted P = 0.027; 2.47 ± 0.74 vs. 1.8 ± 0.83, adjusted P = 0.023). Additionally, either allele carriers (-27614 A or -27307 A) were significantly more common in the multi-vessel disease group (n = 54) than in the single-vessel disease group (n = 75). In conclusion, we reported two new polymorphisms in the distal promoter region of the ST2 gene that possibly influence susceptibility to severe CAD. The functional impact of these polymorphisms remains to be determined.
authors.affiliation: Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Andy
authors.initials: A
authors.lastname: Tsapaki
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zaravinos
authors.forename: Stavros
authors.initials: S
authors.lastname: Apostolakis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voudris
authors.forename: Konstantina
authors.initials: K
authors.lastname: Vogiatzi
authors.forename: Georgios E
authors.initials: GE
authors.lastname: Kochiadakis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D003625:Data Collection; D030561:Databases, Nucleic Acid; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface