Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease

Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor γ (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P = .058, 3.41 [0.95–12.22], P = .060 and 5.10 [0.99–26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92–1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99–1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20–2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed

Fabrication and characterization of vacuum deposited fluorescein thin films

Simple vacuum evaporation technique for deposition of dyes on various solid surfaces has been developed. The method is compatible with conventional solvent-free nanofabrication processing enabling fabrication of nanoscale optoelectronic devices. Thin films of fluorescein were deposited on glass, fluorine-tin-oxide (FTO) coated glass with and without atomically layer deposited (ALD) nanocrystalline 20 nm thick anatase TiO2 coating. Surface topology, absorption and emission spectra of the films depends on their thickness and the material of supporting substrate. On a smooth glass surface the dye initially formes islands before merging into a uniform layer after 5 to 10 monolayers. On FTO covered glass the absorption spectra are similar to fluorescein solution in ethanol. Absorption spectra on ALD-TiO2 is red shifted compared to the film deposited on bare FTO. The corresponding emission spectra at {\lambda} = 458 nm excitation show various thickness and substrate dependent features, while the emission of films deposited on TiO2 is quenched due to the effective electron transfer to the semiconductor conduction band.Comment: 24 pages including 5 figure

Genetic Variants of TSLP and Asthma in an Admixed Urban Population

Peer reviewe

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity

Histologic Grade Is Predictive of Incidence of Epidermal Growth Factor Receptor Mutations in Metastatic Lung Adenocarcinoma

Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II–III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II–III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking

Care in the time of COVID-19: impact on the diagnosis and treatment of breast cancer in a large, integrated health care system.

PurposesTo delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20-5/17/20).MethodsBy extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment characteristics of breast cancer patients diagnosed 3/17/20-5/17/20 to those diagnosed 3/17/19-5/17/2019. Outcomes included time from biopsy to consultation and treatment. Comparisons were made using Chi-square or Wilcoxon rank-sum tests.ResultsFewer new breast cancers were diagnosed in 2020 during the SiP period than during a similar period in 2019 (n = 247 vs n = 703). A higher percentage presented with symptomatic disease in 2020 than 2019 (78% vs 37%, p < 0.001). Higher percentages of 2020 patients presented with grade 3 (37% vs 25%, p = 0.004) and triple-negative tumors (16% vs 10%, p = 0.04). A smaller percentage underwent surgery first in 2020 (71% vs 83%, p < 0.001) and a larger percentage had neoadjuvant chemotherapy (16% vs 11%, p < 0.001). Telehealth utilization increased from 0.8% in 2019 to 70.0% in 2020. Times to surgery and neoadjuvant chemotherapy were shorter in 2020 than 2019 (19 vs 26 days, p < 0.001, and 23 vs 28 days, p = 0.03, respectively).ConclusionsDuring SiP, fewer breast cancers were diagnosed than during a similar period in 2019, and a higher proportion presented with symptomatic disease. Early-stage breast cancer diagnoses decreased, while metastatic cancer diagnoses remained similar. Telehealth increased significantly, and times to treatment were shorter in 2020 than 2019. Our system continued to provide timely breast cancer treatment despite significant pandemic-driven disruption