High-Risk Gene for Alzheimerʼs Disease Identified in African-Americans

2013 ◽  
Vol 13 (10) ◽  
pp. 1
Author(s):  
Jamie Talan
Keyword(s):  
High Risk ◽  
African Americans ◽  
Risk Gene

scholarly journals Nebivolol in High-Risk, Obese African Americans With Stage 1 Hypertension: Effects on Blood Pressure, Vascular Compliance, and Endothelial Function

2009 ◽  
Vol 11 (12) ◽  
pp. 720-725 ◽  
Author(s):  
Nadya Merchant ◽  
Charles D. Searles ◽  
Anbu Pandian ◽  
Syed T. Rahman ◽  
Keith C. Ferdinand ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
African Americans ◽  
Endothelial Function ◽  
Vascular Compliance ◽  
Stage 1

Abstract P159: Coronary Artery Calcium Score Improves the Net Reclassification Index of Prevalent Cardiovascular Disease In African Americans: The Jackson Heart Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Joseph Yeboah ◽  
Che L Smith ◽  
Mario Sims ◽  
Ervin Fox ◽  
Yaorong Ge ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
High Risk ◽  
African Americans ◽  
Diagnostic Accuracy ◽  
Coronary Artery Calcium ◽  
Smoking Status ◽  
Jackson Heart Study ◽  
Net Reclassification Improvement ◽  
Heart Study

Background: Prior studies suggest that African Americans (AA) have lower prevalence of coronary artery calcium (CAC) compared to whites, yet CAC has similar ability to predict coronary heart disease (CHD) events. The role of CAC as a screening tool for CHD risk in AA is unclear. We compared the diagnostic accuracy for CHD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AA. Methods: CAC was measured in 2944 participants in the Jackson Heart Study, an NHLBI funded study of AA based in Jackson, MS. Approximately 8% of this cohort had known cardiovascular disease (CVD) defined as prior MI, angina, stroke, PTCA, CABG or PVD. Logistic regression, ROC and net reclassification index (NRI) analysis were used adjusting for age, gender, SBP, total and HDL cholesterol, smoking status, DM and BMI. FRS was calculated and those with DM were classified as high risk. Results: The mean age was 60, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.26 (1.17, 1.35), p< 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p < 0.0001) for prevalent CVD. The FRS classified 30% of the cohort as high risk, 38.5% as intermediate risk and 31.5% as low risk. FRS classfied 51% of subjects with prevalent CVD as high risk. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD (see figure). Conclusion: In AA, the CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC in AA may be useful in identifying individuals at risk of CVD and reclassifying individuals with low and intermediate FRS.

scholarly journals S100 TREATMENT-DEPENDENCE OF HIGH-RISK GENE EXPRESSION SIGNATURES IN DE NOVO FOLLICULAR LYMPHOMA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1
Author(s):  
C. Bolen ◽  
W. Hiddemann ◽  
R. Marcus ◽  
M. Herold ◽  
S. Huet ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Follicular Lymphoma ◽  
De Novo ◽  
Risk Gene ◽  
Gene Expression Signatures

scholarly journals Clustering of known low and moderate risk alleles rather than a novel recessive high‐risk gene in non‐ BRCA1 /2 sib trios affected with breast cancer

2020 ◽  
Vol 147 (10) ◽  
pp. 2708-2716
Author(s):  
Florentine S. Hilbers ◽  
Peter J. Hof ◽  
Caro M. Meijers ◽  
Hailiang Mei ◽  
Kyriaki Michailidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Moderate Risk ◽  
Risk Gene ◽  
Risk Alleles

scholarly journals Timing and Duration of Incarceration and High-Risk Sexual Partnerships Among African Americans in North Carolina

2008 ◽  
Vol 18 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Maria R. Khan ◽  
William C. Miller ◽  
Victor J. Schoenbach ◽  
Sharon S. Weir ◽  
Jay S. Kaufman ◽  
...  
Keyword(s):  
North Carolina ◽  
High Risk ◽  
African Americans ◽  
Sexual Partnerships

Genetic Variation In MYH9 Is Associated with Sickle Cell Disease Nephropathy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1648-1648
Author(s):  
Emmanuel Okocha ◽  
Melanie Garrett ◽  
Karen Soldano ◽  
Laura M. De Castro ◽  
Jude Jonassaint ◽  
...  
Keyword(s):  
High Risk ◽  
African Americans ◽  
Sickle Cell Disease ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Heavy Chain ◽  
Multiple Testing ◽  
Risk Haplotype ◽  
Cell Disease ◽  
Data Set

Abstract Abstract 1648 Background: Renal failure occurs in 5–18% of sickle cell disease (SCD) patients and is a major risk factor for early mortality. However, there is no established method of identifying SCD patients that are at high risk of developing this outcome prior to the appearance of proteinuria, and its pathobiology is not well understood. The non-muscle myosin heavy chain ll-A (MYH9) gene, which encodes the heavy chain of myosin II-A in the podocyte cytoskeleton, has been identified as driving the high risk of focal segmental glomerulosclerosis (FSGS) and end-stage renal disease in African Americans. Methods: We genotyped 26 single nucleotide polymorphisms (SNPs) in the MYH9 gene in 521 unrelated adult (18 – 83 years) SCD patients who had been screened for proteinuria. Logistic regression was used to determine if the SNPs predicted risk for proteinuria among the patients. Results: Of 521 adult SCD patients studied, 140 had proteinuria, while 381 did not. On average, subjects with proteinuria were 6 years older than subjects without proteinuria (p<0.0001). The odds of having proteinuria increased by 1.04 (4.2%) for every one year increase in age, starting at age 18. We found association with proteinuria for 8 SNPs in MYH9, with nominal p values ranging from 0.025 to 0.0001. Two of these SNPs (rs5756129 and rs1005570) had been previously associated with FSGS in African-Americans without SCD (Kopp et al., 2008). Five SNPs remained significant after correcting for multiple testing (p < 0.003) using the method described by Li and Ji (2005), and a risk haplotype significantly associated with proteinuria (p=0.001) was identified. The frequency of proteinuria among individuals who were homozygous for the risk genotype ranged from 40–50% for each of the five SNPs remaining significant after adjusting for multiple testing, while the risk of proteinuria for individuals who did not have that genotype ranged from 20–30%. Glomerular filtration rate was negatively correlated with proteinuria (r = -0.25, p < 0.0001) but was not itself associated with MYH9 SNPs. Although we tested for association of proteinuria with the two most significant BMPR1B SNPs found by Nolan et al. (2007), neither were associated with proteinuria or GFR in age-adjusted analysis of our cohort, although we did observe nominal evidence for association of a different BMPR1B SNP with proteinuria in our data set (rs1434536, p=0.004, age adjusted). To further investigate a possible connection between BMPR1B and MYH9, we performed regression analyses including BMPR1B SNPs (rs1434536, rs2240036 and rs4145993) and the MYH9 haplotype in the models and controlled for age. In these analyses, the MYH9 risk haplotype remained a significant predictor of proteinuria and was only borderline associated with GFR. None of the BMPR1B SNPs were associated with proteinuria or GFR when the MYH9 haplotype was included in the model, suggesting that MYH9 is likely the more important contributor to these processes in our data set. Conclusion: Our data provide additional support for the role of MYH9 in renal dysfunction among African Americans. A specific haplotype appears to be associated with increased risk for proteinuria among patients with SCD. The association of MYH9 with renal dysfunction in SCD provides insight into the pathophysiology of this process and may lead to early identification of patients at risk and, ultimately, to new modes of therapeutic intervention. Disclosures: De Castro: GlycoMimetics: . Telen:GlycoMimetics: Consultancy, clinical trial sponsorship.

Phase II study of total therapy 3 (TT3) with added bortezomib (V) for multiple myeloma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8020-8020 ◽  
Author(s):  
B. Barlogie ◽  
E. Anaissie ◽  
J. D. Shaughnessy ◽  
F. van Rhee ◽  
K. Hollmig ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii Study ◽  
Gene Array ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Risk Gene ◽  
Strong Trend ◽  
Total Therapy ◽  
Experienced Grade

8020 Background: Building on the success of TT2 with OS exceeding a median of 8 yr, TT3 incorporated V into induction and consolidation/maintenance of melphalan (MEL)-based tandem transplants. Methods: Newly diagnosed patients with MM up to age 75 yr (>59 yr, 47%) were enrolled in TT3, consisting of 2 cycles of V, thalidomide, dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide (VTD-PACE) as induction prior to and as consolidation after MEL transplants, followed by maintenance with monthly VTD in year 1 and TD in years 2 and 3. The primary endpoint was complete response (CR). Results: 303 eligible patients were accrued between 02/04 and 07/06; median follow-up is 19 mo. Tandem transplants were completed in 84% with TT3 and 66% with TT2 (p<0.0001) with similar 12-mo TRM (4% v 5%). At 24 mo, 84% v 68% achieved n-CR including 59% v 44% CR (both p<0.0001). 24-mo EFS is superior (83% v 75%, p=0.02; <65 yr: 86% v 76%, p=0.008) while 24-mo OS is still similar (86% v 85%, p=0.44; <65 yr: 88% v 85%, p=0.16). In gene array-based high-risk MM, 24-mo EFS was 62% v 27% (p=0.006) and 24-mo OS was 74% v 43% (p=0.06). Independent adverse parameters for OS with TT3 were LDH>=190 U/L (27%; HR=3.78, p=0.002), high-risk gene array (14%; HR=3.30, p=0.006) and age >=65 yr (29%; HR=2.23, p=0.044). Compared to the T arm of TT2, fewer patients in TT3 experienced grade >2 tremor (3% v 13%, p<0.001), constipation (6% v 14%, p=0.002), syncope (1% v 12%, p<0.001) and thrombo-embolic events (27% v 38%, p=0.004). Conclusion: Compared to TT2, added V and shortened induction in TT3 increased tandem transplant compliance, effected higher CR and n-CR rates and extended EFS with a strong trend for superior OS in high-risk MM in patients <65 yr. TT3 toxicity was reduced in comparison with the T arm of TT2. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document