Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by B. D Mitchell
Total Records ( 2 ) for B. D Mitchell
  K. V Tarasov , S Sanna , A Scuteri , J. B Strait , M Orru , A Parsa , P. I Lin , S Lai , M. G Piras , M Masala , T Tanaka , W Post , J. R O`Connell , D Schlessinger , A Cao , R Nagaraja , B. D Mitchell , G. R Abecasis , A. R Shuldiner , M Uda , E. G Lakatta and S. S. Najjar
 

Background— Pulse wave velocity (PWV), a noninvasive index of central arterial stiffness, is a potent predictor of cardiovascular mortality and morbidity. Heritability and linkage studies have pointed toward a genetic component affecting PWV. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with PWV.

Methods and Results— The study cohort included participants from the SardiNIA study for whom PWV measures were available. Genotyping was performed in 4221 individuals, using either the Affymetrix 500K or the Affymetrix 10K mapping array sets (with imputation of the missing genotypes). Associations with PWV were evaluated using an additive genetic model that included age, age2, and sex as covariates. The findings were tested for replication in an independent internal Sardinian cohort of 1828 individuals, using a custom chip designed to include the top 43 nonredundant SNPs associated with PWV. Of the loci that were tested for association with PWV, the nonsynonymous SNP rs3742207 in the COL4A1 gene on chromosome 13 and SNP rs1495448 in the MAGI1 gene on chromosome 3 were successfully replicated (P=7.08x10–7 and P=1.06x10–5, respectively, for the combined analyses). The association between rs3742207 and PWV was also successfully replicated (P=0.02) in an independent population, the Old-Order Amish, leading to an overall P=5.16x10–8.

Conclusions— A genome-wide association study identified a SNP in the COL4A1 gene that was significantly associated with PWV in 2 populations. Collagen type 4 is the major structural component of basement membranes, suggesting that previously unrecognized cell-matrix interactions may exert an important role in regulating arterial stiffness.

  Y. C Cheng , W. H. L Kao , B. D Mitchell , J. R O'Connell , H Shen , P. F McArdle , Q Gibson , K. A Ryan , A. R Shuldiner and T. I. Pollin
 

Background— Matrix metalloproteinase (MMP)-1 may play a role in cardiovascular disease susceptibility by influencing plaque rupture via its ability to degrade extracellular collagens.

Methods and Results— We performed a genome-wide association analysis of circulating MMP-1 levels using 500 K single-nucleotide polymorphisms (SNPs) to identify genes influencing variation in serum MMP-1 levels in 778 healthy Amish adults. Serum MMP-1 levels, logarithm transformed, and adjusted for age and sex, were screened for association with SNPs using mixed-model variance components to account for familial relatedness. Median MMP-1 level was 3.05 ng/mL (interquartile range: 1.82 to 5.04 ng/mL) with an estimated heritability of 81% (P<0.0001). Serum MMP-1 levels were strongly associated with a cluster of 179 SNPs extending over an 11.5-megabase region on chromosome 11q. The peak association was with rs495366 (P=5.73x10–34), located within the region between MMP-1 and MMP-3 and having a minor allele frequency of 0.36. Two other SNPs within the 11q region, rs12289128 and rs11226373, were strongly associated with MMP-1 levels after accounting for rs495366 (P≤10–7). These 3 SNPs explained 31% of the variance in MMP-1 levels after adjusting for age and sex.

Conclusions— This study provides strong evidence that the serum MMP-1 level is highly heritable and that SNPs near MMPs on chromosome 11q explain a significant portion of the variation in MMP-1 levels. Identification of the genetic variants that influence MMP-1 levels may provide insights into genetic mechanisms of cardiovascular disease.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility