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- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Bolton, Kelly L., et al.
(author)
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Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
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In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
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Journal article (peer-reviewed)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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| 3. |
- Mitchell, Amanda M, et al.
(author)
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HOPELESSNESS THE "ACTIVE INGREDIENT"? ASSOCIATIONS OF HOPELESSNESS AND DEPRESSIVE SYMPTOMS WITH INTERLEUKIN-6
- 2013
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In: International Journal of Psychiatry in Medicine. - : Baywood Publishing. - 0091-2174 .- 1541-3527. ; 46:1, s. 109-117
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Journal article (peer-reviewed)abstract
- Objective: Previous research has revealed a relationship of depressive symptoms and hopelessness with cardiovascular diseases (CVDs) which are associated with elevated levels of interleukin-6 (IL-6). The objective of this study was to explore whether depressive symptoms and hopelessness are independent predictors of IL-6 levels. Method: Hopelessness, depressive symptoms, and IL-6 were measured in 45 Swedish adults (26 women and 19 men; age range: 31-65 years). Two separated linear regressions were conducted with hopelessness and depressive symptoms serving as individual predictors of IL-6. Another regression analysis examined whether the two predictors predict IL-6 when controlling for each other. The regression coefficients of the models with one predictor and with both predictors were compared. Results: As predicted, after adjusting for age, BMI, illness, smoking, and gender, more depressive symptoms and more hopelessness predicted higher IL-6 levels in independent regressions. When controlling for each other, hopelessness, but not depressive symptoms, predicted IL-6 levels. Finally, when controlling for hopelessness, the regression between depressive symptoms and IL-6 level was significantly reduced; however, there was no significant change in the regression between hopelessness and IL-6 level when controlling for depressive symptoms. Conclusions: Thus, these results suggest that depressive symptoms and hopelessness are not independent predictors of IL-6 levels. Future research should explore the interplay of hopelessness and depressive symptoms on other risk factors of CVDs.
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