title: Effect of a COL1A1 Sp1 binding site polymorphism on arterial pulse wave velocity: an index of compliance.
abstract: -Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-alpha1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.6+/-1.6 years). COL1A1 genotypes were determined using polymerase chain reaction and digestion by restriction enzyme Bal1. Arterial pulse wave velocities were measured in 3 segments, aortoiliac (PWVA), aortoradial (PWVB), and aorto-dorsalis-pedis (PWVF), as an index of compliance using a noninvasive optical method. Data were available for 455 subjects. The sample was in Hardy-Weinberg equilibrium with genotype distributions and allele frequencies that were not significantly different from those reported previously. The T allele frequency was 0.22 (95% confidence interval, 0.19 to 0.24). Two hundred eighty-three (62.2%) subjects were genotype GG, 148 (35.5%) subjects were genotype GT, and 24 (5.3%) subjects were genotype TT. A comparison of GG homozygotes with GT and TT individuals demonstrated a statistically significant association with arterial compliance: PWVF 4.92+/-0.03 versus 5.06+/-0.05 m/s (ANOVA, P=0.009), PWVB 4.20+/-0.03 versus 4.32+/-0.04 m/s (ANOVA, P=0.036), and PWVA 3.07+/-0.03 versus 3.15+/-0.03 m/s (ANOVA, P=0.045). The effects of genotype were independent of age, gender, smoking, mean arterial pressure, body mass index, family history of hypertension, and activity scores. We report an association between the COL1A1 gene polymorphism and arterial compliance. Alterations in arterial collagen type 1A deposition may play a role in the regulation of arterial compliance.
authors.affiliation: Division of Cardiovascular Genetics, Department of Medicine, Royal Free and UCL Medical School, London, United Kingdom. D.Brull@ucl.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Brull
authors.forename: L J
authors.initials: LJ
authors.lastname: Murray
authors.forename: C A
authors.initials: CA
authors.lastname: Boreham
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: H E
authors.initials: HE
authors.lastname: Montgomery
authors.forename: A M
authors.initials: AM
authors.lastname: Gallagher
authors.forename: F E
authors.initials: FE
authors.lastname: McGuigan
authors.forename: G
authors.initials: G
authors.lastname: Davey Smith
authors.forename: M
authors.initials: M
authors.lastname: Savage
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: I S
authors.initials: IS
authors.lastname: Young
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001158:Arteries / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology; D015331:Cohort Studies; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011673:Pulsatile Flow / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D016329:Sp1 Transcription Factor; D003094:Collagen; D004247:DNA