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1دورية أكاديمية
المؤلفون: Kruger, Davida F, Kass, Alex, Lonier, Jacqueline, Pettus, Jeremy, Raskin, Philip, Salam, Maamoun, Trikudanathan, Subbulaxmi, Zhou, Keren, Russell, Steven J, Damiano, Edward R, El-Khatib, Firas H, Ruedy, Katrina J, Balliro, Courtney, Li, Zoey, Marak, Martin Chase, Calhoun, Peter, Beck, Roy W
المصدر: Endocrinology Articles
مصطلحات موضوعية: Adolescent, Adult, Aged, Bionics, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Glycated Hemoglobin A, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Aspart, Insulin Lispro, Regular, Human, Middle Aged, Pancreas, Young Adult
الوصف: Objective: To evaluate the insulin-only configuration of the iLet(®) bionic pancreas (BP) using insulin aspart or insulin lispro in adults with type 1 diabetes (T1D). Methods: In this multicenter, randomized, controlled trial, 161 adults with T1D (18-79 years old, baseline HbA1c 5.5%-13.1%, 32% using multiple daily injections, 27% using a pump without automation, 5% using a pump with predictive low glucose suspend, and 36% using a hybrid closed loop system before the study) were randomly assigned 2:1 to use the BP (N = 107) with insulin aspart or insulin lispro (BP group) or a standard-of-care (SC) control group (N = 54) using their usual insulin delivery plus continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 7.6% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% confidence interval -0.6% to -0.3%, P < 0.001). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 11% (2.6 h/d) and mean CGM glucose was reduced by 16 mg/dL with BP compared with SC (P < 0.001). Improvement in these metrics was seen during the first day of BP use and by the end of the first week reached levels that remained relatively stable through 13 weeks. Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose all favored the BP group (P < 0.001). The CGM-measured hypoglycemia was low at baseline (median time <54 mg/dL of 0.21% [3 min/d] for the BP group and 0.11% [1.6 min/d] for the SC group) and not significantly different between groups over the 13 weeks (P = 0.51 for time <70 mg/dL and 0.33 for time <54 mg/dL). There were 7 (6.5% of 107 participants) severe hypoglycemic events in the BP group and 2 events in the SC group (1.9% of 54 participants, P = 0.40). Conclusions: In adults with T1D, use of the BP with insulin aspart or insulin lispro improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia ...
وصف الملف: application/pdf
العلاقة: https://scholarlycommons.henryford.com/endocrinology_articles/131Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:36173236Test
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2دورية أكاديمية
المؤلفون: Puskarich, Michael A, Ingraham, Nicholas E, Merck, Lisa H, Driver, Brian E, Wacker, David A, Black, Lauren Page, Jones, Alan E, Fletcher, Courtney V, South, Andrew M, Murray, Thomas A, Lewandowski, Christopher A, Farhat, Joseph, Benoit, Justin L, Biros, Michelle H, Cherabuddi, Kartik, Chipman, Jeffrey G, Schacker, Timothy W, Guirgis, Faheem W, Voelker, Helen T, Koopmeiners, Joseph S, Tignanelli, Christopher J
المصدر: Emergency Medicine Articles
مصطلحات موضوعية: Adult, Aged, Angiotensin II Type 1 Receptor Blockers, COVID-19, Double-Blind Method, Female, Hospitalization, Humans, Losartan, Lung Injury, Male, Middle Aged, Organ Dysfunction Scores, Respiratory Function Tests, United States
الوصف: Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to ...
وصف الملف: application/pdf
العلاقة: https://scholarlycommons.henryford.com/emergencymedicine_articles/270Test; https://scholarlycommons.henryford.com/context/emergencymedicine_articles/article/1270/viewcontent/puskarich_2022_oi_220109_1646844110.7309.pdfTest
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3دورية أكاديمية
المؤلفون: Russell, Steven J, Beck, Roy W, Damiano, Edward R, El-Khatib, Firas H, Ruedy, Katrina J, Balliro, Courtney A, Li, Zoey, Calhoun, Peter, Wadwa, R. Paul, Buckingham, Bruce, Zhou, Keren, Daniels, Mark, Raskin, Philip, White, Perrin C, Lynch, Jane, Pettus, Jeremy, Hirsch, Irl B, Goland, Robin, Buse, John B, Kruger, Davida F, Mauras, Nelly, Muir, Andrew, McGill, Janet B, Cogen, Fran, Weissberg-Benchell, Jill, Sherwood, Jordan S, Castellanos, Luz E, Hillard, Mallory A, Tuffaha, Marwa, Putman, Melissa S, Sands, Mollie Y, Forlenza, Gregory, Slover, Robert, Messer, Laurel H, Cobry, Erin, Shah, Viral N, Polsky, Sarit, Lal, Rayhan, Ekhlaspour, Laya, Hughes, Michael S, Basina, Marina, Hatipoglu, Betul, Olansky, Leann, Bhangoo, Amrit, Forghani, Nikta, Kashmiri, Himala, Sutton, Francoise, Choudhary, Abha, Penn, Jimmy, Jafri, Rabab, Rayas, Maria, Escaname, Elia, Kerr, Catherine, Favela-Prezas, Ruby, Boeder, Schafer, Trikudanathan, Subbulaxmi, Williams, Kristen M, Leibel, Natasha, Kirkman, M. Sue, Bergamo, Kate, Klein, Klara R, Dostou, Jean M, Machineni, Sriram, Young, Laura A, Diner, Jamie C, Bhan, Arti, Jones, J. Kimberly, Benson, Matthew, Bird, Keisha, Englert, Kimberly, Permuy, Joe, Cossen, Kristina, Felner, Eric, Salam, Maamoun, Silverstein, Julie M, Adamson, Samantha, Cedeno, Andrea, Meighan, Seema, Dauber, Andrew
المصدر: Endocrinology Articles
مصطلحات موضوعية: Adolescent, Adult, Aged, Bionics, Blood Glucose, Blood Glucose Self-Monitoring, Child, Diabetes Mellitus, Type 1, Glycated Hemoglobin A, Humans, Hypoglycemic Agents, Insulin, Insulin Aspart, Insulin Infusion Systems, Insulin Lispro, Middle Aged, Young Adult
الوصف: BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. ...
العلاقة: https://scholarlycommons.henryford.com/endocrinology_articles/129Test; https://libkey.io/36170500Test
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4دورية أكاديمية
المؤلفون: Patel, Sohil H, Poisson, Laila M, Brat, Daniel J, Zhou, Yueren, Cooper, Lee, Snuderl, Matija, Thomas, Cheddhi, Franceschi, Ana M, Griffith, Brent, Flanders, Adam E, Golfinos, John G, Chi, Andrew S, Jain, Rajan
المصدر: Diagnostic Radiology Articles
مصطلحات موضوعية: Adult, Aged, 80 and over, Biomarkers, Brain Neoplasms, Chromosome Aberrations, Chromosomes, Human, Pair 1, Pair 19, Female, Glioma, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Prognosis, Young Adult
الوصف: Purpose: Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on IDH and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes.Experimental Design: MRI scans from the TCGA/TCIA lower grade glioma database (n = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort (n = 82) was analyzed to validate the T2-FLAIR mismatch sign.Results: Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [κ = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [κ = 0.728 (0.538-0.918)], lesion margins [κ = 0.292 (0.135-0.449)], and peritumoral edema [κ = 0.173 (0.096-0.250)]. All 15 cases that were positive for the T2-FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (P < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2-FLAIR mismatch sign [κ = 0.747 (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (P < 0.00001; PPV = 100%, NPV = 76%).Conclusions: Among lower-grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the IDH-mutant, 1p/19q non-codeleted molecular subtype. Clin Cancer Res; 23(20); 6078-85. ©2017 AACR.
العلاقة: https://scholarlycommons.henryford.com/radiology_articles/83Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:28751449Test
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5دورية أكاديمية
المؤلفون: Beck, Roy W, Riddlesworth, Tonya D, Ruedy, Katrina J, Kollman, Craig, Ahmann, Andrew J, Bergenstal, Richard M, Bhargava, Anuj, Bode, Bruce W, Haller, Stacie, Kruger, Davida F, McGill, Janet B, Polonsky, William, Price, David, Toschi, Elena
المصدر: Endocrinology Articles
مصطلحات موضوعية: Adult, Aged, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Drug Administration Schedule, Female, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Insulin, Insulin Infusion Systems, Male, Middle Aged, Treatment Outcome
الوصف: BACKGROUND: The benefit of initiation of insulin pump therapy (continuous subcutaneous insulin infusion; CSII) in patients with type 1 diabetes using continuous glucose monitoring (CGM) has not been studied. We aimed to assess glycaemic outcomes when switching from multiple daily injections (MDI) to CSII in adults with type 1 diabetes using CGM. METHODS: In this multicentre, randomised controlled trial, 75 adults with type 1 diabetes in the CGM group of the DIAMOND trial were randomly assigned via the study website using a computer-generated sequence to continue MDI or switch to CSII, with continuation of CGM, for 28 weeks. The primary outcome was CGM-measured time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L). This study is registered with ClinicalTrials.gov, number NCT02282397. FINDINGS: Between April 14, 2015, and May 5, 2016, 37 participants were randomly assigned to the CGM plus CSII group and 38 participants were randomly assigned to the CGM plus MDI group. The study was completed by 36 (97%) of 37 participants in the CGM plus CSII group and 35 (92%) of 38 participants in the CGM plus MDI group. Mean CGM use was 6·7 days per week (SD 0·8) in the CGM plus CSII group and 6·9 days per week (0·3) in the CGM plus MDI group (p=0·86). No participants in the CGM plus CSII group who completed the trial discontinued CSII. Over the follow-up period, mean time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L) was 791 min per day (SD 157) in the CGM plus CSII group and 741 min per day (225) in the CGM plus MDI group (adjusted mean treatment group difference: 83 min, 95% CI 17-149; p=0·01). Participants in the CGM plus CSII group had a greater reduction in CGM-measured mean glucose (p=0·005) and hyperglycaemia (on four metrics: p=0·007 for >180 mg/dL [>10·0 mmol/L], p=0·02 for >250 mg/dL [>13·9 mmol/L], p=0·04 for >300 mg/dL [>16·6 mmol/L], and p=0·02 for the area under the curve for 180 mg/dL [10·0 mmol/L]), but also an increase in CGM-measured hypoglycaemia ...
العلاقة: https://scholarlycommons.henryford.com/endocrinology_articles/33Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:28711468Test
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6دورية أكاديمية
المؤلفون: Beck, Roy W, Riddlesworth, Tonya, Ruedy, Katrina, Ahmann, Andrew, Bergenstal, Richard, Haller, Stacie, Kollman, Craig, Kruger, Davida F, McGill, Janet B, Polonsky, William, Toschi, Elena, Wolpert, Howard, Price, David
المصدر: Endocrinology Articles
مصطلحات موضوعية: Adult, Aged, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Drug Administration Schedule, Female, Glycated Hemoglobin A, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Outcome Assessment (Health Care), Patient Satisfaction, Time Factors
الوصف: Importance: Previous clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection. Objective: To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections. Design, Setting, and Participants: Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9%. Interventions: Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53). Main Outcomes and Measures: Primary outcome measure was the difference in change in central-laboratory-measured HbA1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks. Results: Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA1c reduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P < .001). At 24 weeks, the adjusted treatment-group difference in mean change in HbA1c level from baseline was -0.6% (95% CI, -0.8% to -0.3%; P < .001). Median duration of hypoglycemia at less than Conclusions and Relevance: Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA1c level during 24 weeks. Further research is ...
وصف الملف: application/pdf
العلاقة: https://scholarlycommons.henryford.com/endocrinology_articles/35Test; https://scholarlycommons.henryford.com/context/endocrinology_articles/article/1026/viewcontent/jama_beck_2017_oi_160152.pdfTest
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7دورية أكاديمية
المؤلفون: Aleppo, Grazia, Ruedy, Katrina J, Riddlesworth, Tonya D, Kruger, Davida F, Peters, Anne L, Hirsch, Irl, Bergenstal, Richard M, Toschi, Elena, Ahmann, Andrew J, Shah, Viral N, Rickels, Michael R, Bode, Bruce W, Philis-Tsimikas, Athena, Pop-Busui, Rodica, Rodriguez, Henry, Eyth, Emily, Bhargava, Anuj, Kollman, Craig, Beck, Roy W
المصدر: Endocrinology Articles
مصطلحات موضوعية: Adult, Aged, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin A, Humans, Insulin Infusion Systems, Male, Middle Aged, Socioeconomic Factors, Young Adult
الوصف: OBJECTIVE: To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA RESULTS: CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively ( CONCLUSIONS: Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.
العلاقة: https://scholarlycommons.henryford.com/endocrinology_articles/18Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:28209654Test
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8دورية أكاديمية
المؤلفون: Rand, Kristin A, Song, Chi, Dean, Eric, Serie, Daniel J, Curtin, Karen, Sheng, Xin, Hu, Donglei, Huff, Carol A, Bernal-Mizrachi, Leon, Tomasson, Michael H, Ailawadhi, Sikander, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn H, Stram, Alex, Van Den Berg, David J J, Edlund, Christopher K, Conti, David V, Zimmerman, Todd, Hwang, Amie E, Huntsman, Scott, Graff, John, Nooka, Ajay, Kong, Yinfei, Pregja, Silvana L, Berndt, Sonja I, Blot, William J, Carpten, John, Casey, Graham, Chu, Lisa, Diver, W R, Stevens, Victoria L, Lieber, Michael R, Goodman, Phyllis J, Hennis, Anselm J M, Hsing, Ann W, Mehta, Jayesh, Kittles, Rick A, Kolb, Suzanne, Klein, Eric A, Leske, Cristina, Murphy, Adam B, Nemesure, Barbara, Neslund-Dudas, Christine, Strom, Sara S, Vij, Ravi, Rybicki, Benjamin A, Stanford, Janet L, Signorello, Lisa B, Witte, John S, Ambrosone, Christine B, Bhatti, Parveen, John, Esther M, Bernstein, Leslie, Zheng, Wei, Olshan, Andrew F, Hu, Jennifer J, Ziegler, Regina G, Nyante, Sarah J, Bandera, Elisa V, Birmann, Brenda M, Ingles, Sue A, Press, Michael F, Atanackovic, Djordje, Glenn, Martha J, Cannon-Albright, Lisa A, Jones, Brandt, Tricot, Guido, Martin, Thomas G, Kumar, Shaji K, Wolf, Jeffrey L, Deming Halverson, Sandra L, Rothman, Nathaniel, Brooks-Wilson, Angela R, Rajkumar, S Vincent, Kolonel, Laurence N, Chanock, Stephen J, Slager, Susan L, Severson, Richard K, Janakiraman, Nalini, Terebelo, Howard R, Brown, Elizabeth E, De Roos, Anneclaire J, Mohrbacher, Ann F, Colditz, Graham A, Giles, Graham G, Spinelli, John J, Chiu, Brian C, Munshi, Nikhil C, Anderson, Kenneth C, Levy, Joan, Zonder, Jeffrey A, Orlowski, Robert Z, Lonial, Sagar, Camp, Nicola J, Vachon, Celine M, Ziv, Elad, Stram, Daniel O, Hazelett, Dennis J, Haiman, Christopher A, Cozen, Wendy
المصدر: Public Health Sciences Articles
مصطلحات موضوعية: Adult, African Continental Ancestry Group, Aged, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Multiple Myeloma, Polycomb Repressive Complex 1, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases, Repressor Proteins, Transmembrane Activator and CAML Interactor Protein
الوصف: BACKGROUND: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. METHODS: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. RESULTS: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 x 10(-7)) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-kappaB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7. CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. IMPACT: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.
العلاقة: https://scholarlycommons.henryford.com/publichealthsciences_articles/191Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:27587788Test
