Sequence variant on 9p21 is associated with the presence of Abdominal Aortic Aneurysm disease but does not have an impact on aneurysmal expansion
ABSTRACT Abdominal aortic aneurysm (AAA) is among a number of vascular disorders to be recently associated with a common allelic variant situated on chromosome 9p21. To further assess the significance of this region of the genome in AAA development, we genotyped the sequence variation tagged by rs10757278 in two geographically independent cohorts of patients and compared them to matched controls. We also assessed the impact of this variant on AAA growth rate in cohorts with a median surveillance period of 3.2 and 4.5 years. Using meta-analysis to combine the findings of both cohorts, we found a significant association between rs10757278-G and the presence of AAA (OR (95%CI) 1.38 (1.04-1.82) P=0.03), an effect size completely consistent with that originally reported. rs10757278 was not significantly associated with altered AAA growth rate in either cohort.
Full-textDOI: · Available from: Steve E Humphries, Jul 05, 2015
- SourceAvailable from: Ashok Kumar Manickaraj[Show abstract] [Hide abstract]
ABSTRACT: The chromosomal region 9p21 has been reported to be associated with myocardial infarction, coronary artery disease (CAD), diabetes, and many other related multifactorial diseases in humans. Although the genome-wide association studies have identified a limited number of single-nucleotide polymorphisms (SNPs) at 9p21 for CAD risk, the role of flanking SNPs has not been studied so far. Therefore, in the present work, we studied the role of flanking SNPs with respect to that of the previously identified SNPs rs10757278 and rs2383207 at 9p21 among the Indian subjects found to have CAD (n = 414) along with age- and sex-matched control subjects (n = 408). Our study replicated the association of genome-wide association studies that had identified SNPs rs2383207 (p = 4.7 × 10(-5)) and rs10757278 (p = 5.5 × 10(-5)) among Indians with CAD. Further, we evaluated nine additional SNPs, of which two SNPs flanking rs2383207 (rs1537375 [p = 2.4 × 10(-5)] and rs1537374 [p = 5.6 × 10(-5)]) were also strongly associated with CAD. The haplotypes constructed using four risk SNPs revealed that the haplotypes with combinations of rs10757278 showed CAD risks, whereas the minor alleles of rs2383207, rs1537375, and rs1537374 in combinations reduce the CAD risks substantially. Our study demonstrates that the variation in the chromosomal region 9p21 is involved in modifying progression toward CAD among Indians and the risk may be variable, contributed by the SNPs that are flanking previously identified SNPs.DNA and cell biology 02/2011; 30(2):105-10. DOI:10.1089/dna.2010.1046
- [Show abstract] [Hide abstract]
ABSTRACT: With the advent of the genome-wide association (GWA) study, a promising new avenue for identifying genetic markers for complex diseases like coronary artery disease (CAD) has been opened. This avenue, however, is not without challenges and limitations, including the need for carefully designed and executed studies and the risk of false positive associations. Nonetheless, new markers have been identified through such studies that could potentially revolutionize the ways that individuals with CAD are identified and managed.American Journal of Translational Research 01/2009; 1(3):221-34.
Conference Paper: Direct manipulation user interfaces based on constraints[Show abstract] [Hide abstract]
ABSTRACT: Object-oriented user interface technology increases the productivity of interface designers and programmers. However, there are some shortcomings to the object-oriented approach. An approach that is based on the concept of separating the presentation from the application data is presented. While in object-oriented user interfaces presentation and application data communicate via a protocol of procedure cells, in this approach the relationships are described declaratively with structured sets of maintained constraints. An overall architecture based on constraints that encompasses all aspects of a user interface is described. The procedural behavior of a user interface is achieved through constraint satisfactionComputer Software and Applications Conference, 1989. COMPSAC 89., Proceedings of the 13th Annual International; 10/1989