[Ten-year survival after off-pump coronary artery bypass grafting compared with traditional bypass grafting]. / Cirugía de revascularización miocárdica: comparación de supervivencia a 10 años de la cirugía coronaria con y sin circulación extracorpórea mediante Propensity Score Matching.

BACKGROUND: Long-term outcomes of Off-Pump Coronary Artery Bypass Grafting (OPCAB) as an alternative to the traditional Coronary Artery Bypass Grafting (CABG) technique with cardiopulmonary bypass (CPB) are not well defined. AIM: To compare 10-year survival of isolated OPCAB versus CABG with CPB. MATERIAL AND METHODS: Analysis of information obtained from databases, clinical records and surgical protocols of patients treated with isolated CABG between January 2006 and November 2008 at a Regional Hospital. Of 658 isolated CABG, 192 (29.2%) were OPCAB and 466 (79.9%) CPB. Propensity Score Matching (PSM) was performed to compare both groups. After PSM, two groups of 192 cases were obtained. Mortality data was obtained from the Chilean public identification service. Ten-year survival was calculated and compared with Kaplan-Meier and log-rank methods. RESULTS: Follow-up data was obtained in all cases. No statistically significant differences were found when comparing 10-year survival between OPCAB versus CPB (78.6% and 80.2% respectively, p 0.720). There was also no statistical difference in cardiovascular death free survival (90.1% with CPB versus 89.1% OPCAB, p 0.737). Survival was comparable when analyzing subgroups with diabetes mellitus, left ventricular dysfunction or chronic kidney disease, among others. CONCLUSIONS: In our series, OPBAB has a comparable 10-year survival with CABG with CPB.

[Lung cancer at a Chilean public hospital]. / Cáncer pulmonar: caracterización, estadificación y supervivencia en una cohorte de una década en un hospital del sistema público de salud de Chile.

BACKGROUND: Lung cancer is the world's leading cause of cancer death. AIM: To describe the clinical, staging and survival characteristics of lung cancer in a public Chilean regional hospital. MATERIAL AND METHODS: Analysis of a prospective database of a thoracic surgery service, retrieving histologically confirmed lung cancer cases from January 2010 to December 2019 and reviewing their medical records. Cases were re-staged by the TNM-8 system and variables were compared between periods 2010-2014 and 2015-2019. RESULTS: We retrieved 551 lung cancer cases, 333 (60 %) men, with a mean age of 65 years. Distant metastases were found in 72% of cases (excluding lymphatic metastases). Of the non-small cell lung cancers (NSCLC), 50 (10%) cases were in stage I, 18 (4%) in stage II, 81 (16%) in stage III and 347 (70%) in stage IV. Global five-year survival was 18%, 20% for NSCLC, 71% for excised NSCLC, 8% for non-excised NSCLC, 88% for stage I and 92% for subgroup IA. Resective surgery was performed in 81 (14%) cases. When comparing 2010-2014 and 2015-2019 periods, the frequency of resective surgery increased from 7% to 20%. CONCLUSIONS: The diagnosis of lung cancer was frequently made in advanced stages. There was a significant increase in early diagnosis and frequency of surgeries with curative intent in the second observation period.

[Risk factors associated with 10-year survival after coronary artery bypass grafting]. / Enfermedad coronaria: factores de riesgo y supervivencia a 10 años en la cirugía coronaria.

BACKGROUND: Coronary artery bypass grafting (CABG) is the treatment of choice for a broad spectrum of patients with coronary disease. AIM: To describe global survival and factors associated with lower long-term survival in patients operated with isolated CABG. MATERIAL AND METHODS: Analysis of a cohort of patients who underwent CABG between January 2006 and December 2008 at a public hospital. The database and operation records of 1.003 cardiac surgeries were reviewed. Of these, an isolated CABG was performed in 658 patients aged 62 ± 9 years including 516 male (78%). Survival data were obtained from the Chilean Civil Registry Office and a complete ten-year follow up was accomplished. Survival was analyzed with Kaplan-Meier method with log-rank test and Cox regression. RESULTS: Operative mortality occurred in 13 patients (2%). Survival at 1, 3, 5 and 10 years was 97, 94, 91 and 76%, respectively. One, 3, 5 and 10-year free of cardiovascular death survival was 98, 97, 95 y 89%, respectively. Factors associated with long-term survival were chronic kidney disease in hemodialysis (Hazard ratio (HR) 7.9; 95% confidence intervals (CI) 4.6-13.6), chronic obstructive pulmonary disease (HR 2.3; 95% CI 1.4-3.7), chronic arterial occlusive disease (HR 2.2; 95% CI 1.4-3.4) and diabetes mellitus (HR 1.9; 95% CI 1.4-2.6). According to EuroSCORE, 10-year survival was 86, 75 and 62% (p < 0.01) in low, medium and high-risk patients, respectively. CONCLUSIONS: These patients had a 10-year survival comparable to large international series. Groups associated with lower 10-year survival were identified.

[Reconstruction of aortic valve using Ozaki technique. Report of two cases]. / Reconstrucción de válvula aórtica con pericardio autólogo según técnica de Ozaki.

Prosthetic valve replacement is the standard treatment for aortic valvulopathy. Due to the structural valve deterioration of biological prosthesis and the anticoagulation requirements of mechanical valves, the repair of aortic valve disease is receiving more attention in recent years. The Ozaki technique consists in the reconstruction of a trileaflet valve using autologous pericardium. We report our first two cases of successful reconstruction of the aortic valve using this technique with 12-month echocardiographic and 24-month clinical follow up.

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study.

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

[Primary cardiac tumors. Experience in 72 cases]. / Tumores cardíacos primarios.

BACKGROUND: Primary cardiac tumors have a low incidence, and their presentation form and clinical course are not well known. AIM: To describe the characteristics, treatment, follow up and survival of patients with primary cardiac tumors (PCT). MATERIAL AND METHODS: Review of all surgical procedures for PCT performed between 1984 and 2019 in a regional general hospital. The information was obtained from surgical protocols, surgical and pathology databases, medical records and registries of the Chilean National Identification Service. The clinical features of patients, immediate and long term outcomes are described. RESULTS: Seventy-two surgical procedures for PCT were reviewed. Patients' age was 55 ± 15 years and 60% were women. The most common histological types were myxoma in 49 patients (68%), papillary fibroelastoma in 13 (18%) and sarcoma in 6 (8.3%). Forty-nine (68.1%) were symptomatic and all tumors were found on echocardiography. Fifty-one (71%) were in the left atrium, 10 (14%) in the aortic valve and eight (11%) in the right atrium. The surgical procedures were tumor resection in 48 patients (67%) and resection and repair with patch in 23 (32%). Mean postoperative stay was 6.6 ± 4.4 days, eight patients (11%) had complications and no patient died in the immediate postoperative period. Long term survival was higher in patients with benign PCT as compared with those with malignant tumors. CONCLUSIONS: Most PCTs in this group of patients were benign neoplasms and the most common tumors were myxomas. The main diagnostic method is echocardiography and the prognosis of surgical treatment is excellent when the tumors are benign. (Rev Med Chile 2020; 148: 327-335).

[Features of pulmonary hydatidosis in 368 patients admitted to a regional hospital]. / Hidatidosis pulmonar: características, manifestaciones clínicas y tratamiento en pacientes hospitalizados en Concepción, Región del Biobío, Chile.

BACKGROUND: Lungs are the second location in frequency of hydatidosis or cystic echinococcosis. AIM: To characterize the clinical manifestations, diagnosis, findings and treatment of patients hospitalized for a pulmonary hydatid cyst (PHC). MATERIALS AND METHODS: Review of databases, medical records, operation notes and death certificates of patients admitted to a Chilean regional hospital with a PHC. RESULTS: Four hundred twenty-nine cases were identified and complete data was obtained from 368 patients aged 34 ± 19 years, 224 (60,9%)men. The most common clinical manifestations were cough in 269 (73%) and chest pain in 217 (59%). The most frequent locations were the right lung in 210 (57%) and lower lobes in 218 (59%). One hundred eighty-seven cysts (51%) were complicated. Conservative surgery (cystectomy) was performed in 308 (84%). Postoperative morbidity was observed in 77 (21%) and mortality in 6 (2%) patients. Recurrence was observed in 28 (8%) patients. There was a significant reduction in morbidity, mortality, reoperations, and postoperative days over time. CONCLUSIONS: In these patients, pulmonary hydatidosis was diagnosed mainly during working ages and half of patients had a complicated cyst.

[Embolic stroke secondary to a mitral valve fibroelastoma. Case report]. / Accidente cerebrovascular embólico secundario a fibroelastoma papilar de válvula mitral.

Embolic stroke secondary to cardiac tumors is uncommon. However, 25-30% of cardiac tumors may cause systemic emboli. We report a 29-year-old male consulting for a sudden episode of aphasia and right hemiparesis, compatible with infarct of the left middle cerebral artery territory. Transthoracic echocardiography reported an ovoid tumor of 8 × 7 × 7 mm in relation to the sub valvular apparatus of the mitral valve. After neurologic stabilization, surgical treatment was performed. Approached by median sternotomy and in cardiopulmonary bypass, the mitral valve was explored. A macroscopic tumor consistent with a papillary fibroelastoma curled in sub valvular chordae was found. It was deployed and resected from its base, while the anterior mitral leaflet was preserved intact. Histopathological examination confirmed the intraoperative macroscopic diagnosis. The patient recovered uneventfully postoperatively and was discharged on the fifth day after surgery. He currently is in functional capacity I without cardiovascular symptoms at five years follow-up.

Short-Term Effects on Agricultural Soils Irrigated with Reclaimed Water in Baja California, México.

In 2014 reclaimed water (RW) started to be used for agricultural irrigation of 200 ha in Maneadero Valley, Baja California, Mexico. The RW had relatively high electrical conductivity (4-5 dS m-1), and K+, Mg2+, PO43- and Cl- concentrations relative to irrigation guidelines. However, no accumulation of these elements, nor total nitrogen, was observed in the studied soils. The main effect of RW irrigation was the downcore leaching of Cl- and Na+ below 120 cm, causing an increase in electrical conductivity in the lower soil horizons. Al, Fe and Zn showed a twofold to eightfold accumulation in the top soil layer after 2 years. Moderate to severe chemical clogging of dripping systems and potential biological clogging are likely to occur. Mexican national guidelines for the reuse of RW do not take into account specific variables that could change the quality of agricultural soil or lead to clogging of drip irrigation systems.

[Early and late results of coronary artery bypass grafting in coronary artery disease in Concepcion, Chile]. / Cirugía coronaria: resultados inmediatos y alejados de la cirugía de revascularización miocárdica en enfermedad coronaria.

BACKGROUND: Coronary artery bypass grafting (CABG) is the best treatment for a large group of patients with coronary artery disease. AIM: To describe early and late results of patients treated with CABG at our Center. PATIENTS AND METHODS: Revision of data bases, surgical protocols and clinical registers of patients operated between January 2006 and December 2008. RESULTS: Of 1.003 cardiac surgeries performed during the period, 658 corresponded to isolated CABG (78% in men). The median age of patients was 62 years. Left common coronary artery lesions was found in 135 cases (20%), 555 patients (84%) had hypertension and 231 (35%) were diabetics. Four-hundred thirty (65%) had stable angina and 211 (32%) had a recent myocardial infarction. Twenty-two had left ventricular ejection fraction < 30%. In 248 (38%), a low Additive EuroSCORE risk was found. Emergency surgery was required in 36 (6%) patients. Use of extracorporeal circulation was required in 466 patients (71%). Within 30 days of surgery, complications were recorded in 105 patients (16%) (15 (2%) stroke, 14 (2%) myocardial infarction, 7 (1%) mediastinitis, and in 14 (2%) a reoperation for bleeding). Thirteen patients died (2%). Among the 303 patients with stable angina and preserved left ventricular function, two died (0,7%). Survival at 1, 3 and 5 years was 97,4%, 93,8% y 90,9% respectively. Major adverse cardiac and cerebrovascular events at five years occurred in 20%, stroke in 4%, myocardial infarction in 3% and reintervention in 2%. Seven percent of patients had recurrence of angina. CONCLUSIONS: We describe a heterogeneous series of patients. The immediate and late results are comparable with international communications.

[Results of extended transsternal thymectomy for Myasthenia gravis. Experience with 58 patients]. / Miastenia gravis: resultados inmediatos y alejados de la timectomía transesternal extendida.

BACKGROUND: Thymectomy improves clinical outcomes and decreases the need for medical treatment in patients with myasthenia gravis (MG). AIM: To describe the immediate and long-term results of extended transsternal thymectomy (ETT) in patients with MG. MATERIAL AND METHODS: A review of databases, surgical protocols, clinical records and interviews of patients subjected to extended transsternal thymectomy for MG between 1990 and 2016. Perioperative clinical characteristics, anticholinesterase treatment, immediate and remote surgical results were analyzed and patients were followed from one to 10years. RESULTS: We studied 58 patients aged 35 ± 14years (72%) women. In the preoperative period, according to Osserman classification, nine patients (15,5%) were in grade I, eight (13,8%) in grade IIA 8 and 40 (69%) in grade IIB. The pathological study of the surgical piece showed thymic hyperplasia in 39 cases (67,2%). Four patients had postoperative complications but none died. In the Follow-up at 1, 3, 5, 8 and 10years the Masaoka palliation rate was 71.7, 77.5, 67.7, 70.0 and 70,6% respectively. The figures for remission rate were 13.0, 15.0,19.4, 35.0 and 35,3% respectively. The figures for Zielinski positive results were 79.6, 87.5, 87.1, 90.0 and 82,4% respectively. The DeFilippi score improved by 80.4, 87.5, 87.1, 90.0 and 82.4% respectively. The Myasthenia Gravis Foundation of America Post-Intervention State improved by 67.4, 77.5, 77.5, 75.0 and 70,6% respectively. Mean Myasthenia Gravis Activities of daily living (MGADL) and Myasthenia Gravis Quality of life scale 15 (MGQOL 15) were 1.65 and 6.31 respectively. CONCLUSIONS: In selected patients with MG, extended transsternal thymectomy in MG has good immediate and long-term results.

[Thoracic trauma. Experience of three decades]. / Traumatismo torácico: caracterización de hospitalizaciones durante tres décadas.

BACKGROUND: Trauma is the leading cause of death in young patients and thoracic trauma (TT) is responsible for 25-35% of trauma deaths. AIM: To describe and compare features, trauma severity indexes and morbidity of patients admitted for TT in the past three decades. MATERIAL AND METHODS: Review of a TT database, operative notes and medical records of patients. These were separated by decade of admission (1981-1990, 1991-2000, 2001-2010). TT characteristics were compared. Injury Severity Score (ISS), Revised Trauma Score (RTS-T) and Trauma Injury Severity Score (TRISS) were calculated. RESULTS: A total of 3,068 TT were reviewed. In the 1981-1990 period, 604 cases of TT were registered (19.7%), in the 1991-2000 period, 1,070 cases (34.9%) and in the 2001-2010 period, 1,394 cases (45.4%) (p < 0.05). The ages of patients in each of these periods were 34.9 ± 15.5, 33.9 ± 16.2 and 35.7 ± 18.2 years respectively (p < 0.05). The proportion of patients aged 65 years or more were 6.6, 7.7 and 10.1% respectively, the proportion of females was 6.1, 9.4 and 12.0%, respectively. The causing agents per decade were knife wounds in 51.5, 61.1 and 60.0% of cases respectively, firearms in 2.5, 3.3 and 5.0% of cases respectively, multiple trauma in 13.9, 14.5 and 9.0% respectively and morbidity in 18.7, 19.7 and 11.7%, respectively. The ISS per decade was 11.9 ± 6.5, 12.9 ± 6.9 and 10.4 ± 6.8 respectively. No significant difference were found in mortality (1.5, 3.0, 2.0% respectively) or TRISS score (2.7, 3.2 and 3.8% respectively). CONCLUSIONS: An increase in the number of hospital admission for TT has occurred in the last three decades, with an increase in the proportion of admissions of subjects aged 65 years or more, females and with firearm injuries.

Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain.

BACKGROUND: Invasive fungal infections (IFI) are associated with significant morbidity and mortality. The objective of this work was to compare the costs per adult patient, associated with intravenous isavuconazole (ISAV) followed by oral ISAV versus the regimen of liposomal amphotericin B followed by posaconazole (L-AMB→POSA) in the treatment of IFI. The comparison was conducted from the perspective of the Spanish National Health System (SNS). METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration, hospitalization, laboratory tests and adverse events costs were evaluated from SNS perspective. Deterministic and probabilistic sensitivity analyzes were performed. RESULTS: Total costs per-patient were €24,715.54 with ISAV versus €29,753.53 with L-AMB→POSA, resulting in cost-savings per patient treated with ISAV of €5,037.99 (-16.9%). Treatment costs of IFI remained lower for ISAV than for L-AMB→POSA across all sensitivity analyses (-7,968.89€ to -326.59€), being treatment duration the most influential parameter. CONCLUSION: According to the present model, the treatment of IFIs with ISAV would generate savings for the SNS compared to L-AMB→POSA. These savings are attributed to the shorter duration of IV treatment, reduced use of healthcare resources and lower costs associated with managing adverse effects when ISAV was employed.

Treatment of vitiligo with a chimeric monoclonal antibody to CD20: a pilot study.

Five patients with active disseminated vitiligo were given 1g of a chimeric (murine/human) monoclonal antibody to CD20 in a single intravenous infusion and followed-up for 6 months. Three of the patients showed an overt clinical and histological improvement of the disease, one presented slight improvement and the remaining patient showed no changes. Improvement was neither associated with changes in laboratory parameters nor to a specific human leucocyte antigen D-related (HLA-DR) phenotype. We believe that these preliminary results are encouraging, and further clinical trials should be undertaken. An important aim should be the finding of a marker with a good response to this therapeutic approach.

[Off-pump coronary surgery. Experience in 220 patients]. / Resultados inmediatos y a mediano plazo de la cirugía coronaria sin circulación extracorpórea.

BACKGROUND: Coronary artery bypass graft surgery without cardiopulmonary bypass (CPB) is an alternative technique for myocardial revascularization. AIM: To report the early results and 4 years follow up of the first 220 cases operated with this technique. PATIENTS AND METHODS: Descriptive study of 220 patients aged 60.6 ± 8.8 years (171 men) undergoing off-pump coronary surgery between 2004 and 2008. One hundred seventy six (80%) patients had hypertension, 59 (26.8%) had diabetes, 86 (39%) dyslipidemia and 85 (38.6%) were smokers. One hundred forty one patients (64.1%) had stable angina. Fifty four (24.5%) had a recent infarction (< 90 days) and 46 (20.9%) had a previous angioplasty. Ejection fraction was < 30% in 9 (4.1%), 30% - 50% in 57 (25.9%) and > 50% in 154 (70%). Additive and logistic EuroSCORE were 3.32 and 3.55% respectively. We studied the complications and mortality at 30 days. Long term follow up (late mortality and major cardiovascular events such as myocardial infarction (MI) stroke and re-intervention were assessed using data of medical records and National Identification Registry Service until June 30, 2011. RESULTS: A total of 481 bypasses were performed (2.27 bypasses l patient). There were 4 (1.8%) conversions and no incomplete revascularization. Post-Operative complications occurred in 42 patients. Eight neurological (five strokes), five renal (two required dialysis), 16 cardiovascular (four myocardial infarctions), 15 surgical and 11 infections. Three patients died (1.36%). After a follow up of 4.26 ± 1.02 years, overall survival was 92.3%, and survival free of myocardial infarction, stroke or re - intervention was 96.8%, 96.8% and 95.9% respectively. CONCLUSIONS: Off-pump coronary surgery in selected patients has immediate and late results comparable to traditional surgery.

[Doege-Potter syndrome: hypoglycemia secondary to solitary fibrous tumor of the pleura. Report of one case]. / Síndrome de Doege-Potter: hipoglicemia secundaria a tumor fibroso solitario de la pleura.

Doege-Potter syndrome is characterized for hypoglycemia associated with solitary pleural fibrous tumors. We report a 38-year-old woman with a history of weight loss, malaise and edema. After an episode of symptomatic hypoglycemia, she was admitted to the hospital, where she had new episodes of hypoglycemia. A Chest X ray and scan showed a right pleural tumor that was surgically excised. After surgery the episodes of hypoglycemia subsided. The pathological study of the tumor revealed a solitary fibrous pleural tumor. After 15 months of follow up, the patient is symptom free and without evidence of tumor relapse.

Pyrogallol red oxidation induced by superoxide radicals: application to evaluate redox cycling of nitro compounds.

The bleaching of the pyrogallol red (PGR) dye mediated by superoxide anion radicals (O(2)(-)) generated from the xanthine/xanthine oxidase system (X/XO) was studied by UV-visible spectrophotometry. The absorption band (at 540 nm) of PGR quickly decreased in the presence of X/XO, implying an efficient reaction of O(2)(-) with PGR. The process was unaffected by catalase (CAT), but completely abolished by superoxide dismutase (SOD). A mechanism of the reaction involving the consumption of one PGR molecule by two O(2)(-) to generate one molecule of H(2)O(2) is proposed. PGR was used as a probe to estimate the rate of O(2)(-) generation in redox cycling reactions of a series of nitro compounds mediated by rat liver microsomes. The consumption of PGR induced by the redox cycling of nitrofurantoin was totally eliminated by the addition of SOD but unaffected by CAT. The initial rate of consumption of PGR mediated by the redox cycling of others nitro derivatives follows the order: furazolidindione > nitrofurantoin > nifurtimox > benznidazole > chloramphenicol. We concluded that PGR can be used as a probe to estimate the release of O(2)(-) from enzymatic systems or from the redox cycling of nitro compounds.

Transdermal penetration of diclofenac in the presence of AAPH-derived peroxyl radicals.

In vitro transdermal delivery of diclofenac across pig skin in the presence of AAPH-derived peroxyl radicals (2,2'-azo-bis(2-amidinopropane)dihydrochloride) has been studied. The transdermal absorption of diclofenac was estimated using high-performance liquid chromatography after its incubation in vertical cells. The diclofenac transdermal penetration was highly modified by peroxyl radicals. In the presence of AAPH, lower diclofenac absorption was observed. This effect was inhibited by ferulic acid. This could be explained by diclofenac-peroxyl radical interactions. In the pretreatment skin with AAPH, lower diclofenac absorption was higher than control experiments. This behavior should be considered in the topical administration of pharmaceutical preparations containing diclofenac.

Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.

African Americans (AAs) are an admixed population with widely varying proportion of West African ancestry (WAA). Here we report the correlation of WAA to gene expression and DNA methylation in AA-derived hepatocytes, a cell type important in disease and drug response. We perform mediation analysis to test whether methylation is a mediator of the effect of ancestry on expression. GTEx samples and a second cohort are used as validation. One hundred and thirty-one genes are associated with WAA (FDR < 0.10), 28 of which replicate and represent 220 GWAS phenotypes. Among PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19, and P2RY1 nominally associate with WAA (p < 0.05). We find 1037 WAA-associated, differentially methylated regions (FDR < 0.05), with hypomethylated genes enriched in drug-response pathways. In conclusion, WAA contributes to variability in hepatocyte expression and DNA methylation with identified genes previously implicated for diseases disproportionately affecting AAs, including cardiovascular (PTGIS, PLAT) and renal (APOL1) disease, and drug response (CYP2C19).