Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nature Genetics (Impact Factor: 29.65). 07/2012; 44(8):890-4. DOI: 10.1038/ng.2337
Source: PubMed

ABSTRACT We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

Download full-text


Available from: Xiangfeng Lu, Jul 03, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd's ratio OR=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08-1.14) and MI (RR=1.14; 95%CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.Journal of Investigative Dermatology accepted article preview online, 19 January 2015. doi:10.1038/jid.2015.8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prevention of coronary artery disease (CAD) is an appropriate goal for the 21st century. Randomized clinical studies consistently show a 30-40% reduction in mortality and morbidity by modifying known risk factors. However, genetic risk, estimated to account for 40-60% of susceptibility to CAD, has until recently been unknown. Comprehensive prevention will require knowledge of both. The 21st century technology has responded to the challenge. Whereas the first genetic risk variant was not discovered until 2007 (9p21), a total of 36 genetic risk factors for CAD have been discovered and verified in large sample sizes. A startling discovery was that over two-thirds of these factors do not act through known risk factors or mechanisms. This obviously has great implications for the pathogenesis of CAD and presents many potential targets for new therapy. These genetic risk factors occur more commonly in the population than expected, with over half of them occurring in more than 50% of the population, and 10 of them occurring in at least 75% of the population. The role of genetic risk factors in genetic screening for prevention of heart disease is yet to be defined. The technology is already available, but functional analysis may be a prerequisite for their clinical application.
    Current opinion in cardiology 02/2012; 27(3):221-7. DOI:10.1097/HCO.0b013e3283515b4b · 2.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. RESULTS: Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H2O2) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H2O2. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H2O2-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H2O2-treated cells. CONCLUSIONS: In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells.
    BMC Neuroscience 12/2012; 13(1):149. DOI:10.1186/1471-2202-13-149 · 2.85 Impact Factor