Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands. Furthermore, several genomic regions showed significant and large deviations in African or European ancestry and were significantly enriched in genes involved in prevalent diseases in this community, such as diabetes, asthma, and allergy. The most prominent of these regions were located near LCT and the HLA, two well-known targets of selection, at which 40‒50% of the Canarian genome is of recent African descent according to our estimates. Putative selective signals were also identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9 genes. Taken together, our findings provide solid evidence of a significant recent African admixture, population isolation, and adaptation in this part of Europe, with the favoring of African alleles in some chromosome regions. These findings may have medical implications for populations of recent African ancestry.

Recurrent episodes of bradykinin-mediated angioedema (Bk-AE) can associate with acquired or hereditary conditions, the former most commonly developing secondarily to a pharmacological treatment. Despite successful genomic advances that have led to the identification of a large number of disease genes irrespective of disease prevalence, their application to Bk-AE has barely occurred. As a consequence, the genetic causes of Bk-AE remain poorly understood, obstructing the identification of patient subtypes and the development of precision medicine strategies. This review provides an update of the genetic studies completed to date on the acquired forms, which have almost exclusively focused on Bk-AE secondarily to the angiotensin-converting enzyme inhibitor treatment, and the blooming subdivision of the hereditary forms established by the identification of novel causal genes with next-generation sequencing (NGS) technology-based exome studies in genetically undiagnosed patients. Finally, based on the diverse benefits that are offered by the technology, we present arguments favoring the use of holistic NGS approaches as first-tier genetic tests as a promise to reduce the diagnostic odyssey of patients with suspected hereditary forms of Bk-AE.

Objective: To analyse the association between serum C-peptide and coronary artery disease in the general population. Methods: Follow-up study of 6630 adults from the general population. They were stratified into group 1 (no insulin resistance: C-peptide < third tercile and glycaemia < 100 mg/dL), group 2 (initial insulin resistance: C-peptide ⩾ third tercile and glycaemia < 100 mg/dL) and group 3 (advanced insulin resistance: glycaemia ⩾ 100 mg/dL). Results: After 3.5 years of follow-up, group 2 had a higher incidence of myocardial infarction (relative risk (RR) = 4.2, 95% confidence interval (CI) = 1.7-10.6) and coronary artery disease (RR = 3.5, 95% CI = 1.9-6.6) than group 1. Group 3 also had increased incidences of both diseases. In multivariable analysis of the entire population, groups 2 and 3 showed significant risks of myocardial infarction and coronary artery disease (RR > 3 and RR > 2, respectively). However, when people with diabetes were excluded, the increased risks were corroborated only in group 2 for myocardial infarction (RR = 2.8, 95% CI = 1.1-6.9; p = 0.025) and coronary artery disease (RR = 2.4, 95% CI = 1.3-4.6; p = 0.007). Conclusion: Elevated C-peptide is associated with the incidence of myocardial infarction and coronary artery disease in the general population. It can be an earlier predictor of coronary events than impaired fasting glucose.

AimResistin is a cytokine related with inflammation and ischemic heart disease. Physical activity (PA) prevents chronic inflammation and ischemic heart disease. We studied the relationship of serum concentration of resistin with HDL cholesterol, a known biomarker of PA, and with different measures of PA, in a large sample of the general adult population in the Canary Islands.MethodsCross-sectional study of 6636 adults recruited randomly. We analyzed the correlation of resistin and HDL cholesterol with PA (as metabolic equivalent level [MET]), and fitted the results with linear and logistic regression models using adjustment for age, alcohol consumption and smoking.ResultsMean resistin level was higher in women (p<0.001), correlated inversely with age, HDL cholesterol (p<0.001) and alcohol consumption (p<0.001 in men), and correlated directly with smoking (p<0.001). Resistin correlated inversely with the duration of leisure time PA (p<0.001), leisure time MET (p<0.001) and moderate leisure time PA (p<0.001), with some differences between sexes. Men (OR = 0.78 [0.61–0.99; p<0.05]) and women (OR = 0.75 [0.61–0.92; p<0.01]) in the upper quintile of leisure time PA had a lower risk of elevated resistin. In contrast, a high degree of sedentarism was associated with an increased risk elevated resistin in women (OR = 1.24 [1.04–1.47; p<0.05] and in men (OR = 1.40 [1.01–1.82; p<0.05]).ConclusionsIn our sample of the general population, resistin was inversely associated with measures and levels of PA and HDL cholesterol. The association of resistin with PA was stronger than the association of HDL cholesterol with PA, making resistin a potentially useful biomarker of PA.

Introduction Little is known on how the domain and intensity of physical activity (PA) associates with metabolic syndrome (MetS). The aim of this study was to examine associations between PA domains (leisure-time, domestic, active transport, total walking and total PA), PA intensities (light, moderate and vigorous) and PA levels with MetS in the general adult population. Methods Cross-sectional study. Anthropometry, blood biochemistry, 79-item PA-questionnaire, lifestyle and medical history were evaluated in a representative sample of Canary Island adults (n = 6,729). MetS was diagnosed using the harmonized IDF-NHLBI-AHA criteria. T-test and multivariable logistic regression was used to analyse associations between PA domains and intensities with MetS vs . no MetS, controlling for socio-demographic, lifestyle, family antecedents and body mass index (BMI). Results For each MET-h/day spent in moderate-vigorous PA intensities, as well as in recreational domain, active transport, total walking and total PA, the odds of MetS decreased between 3–10%. Energy expenditure exclusively in light and domestic PAs was not associated with MetS, however it was important to achieve a total PA level of 3 MET-h/day, which reduced the odds of MetS by 23%. This reduction was blunted in those with more than 2 h/d of TV watching time. A PA level of 3 MET-h/d also nullified the risk of MetS in those with low PA and high TV consumption. Conclusions Some types of leisure time PAs may contribute more than others to reducing MetS. Light and domestic PA play a complementary role in enhancing energy expenditure in the general population. TV watching time above 2 h/d counteracted the MetS risk reduction associated with PA level, but PA level also reduced the risk of METs presented by those with a low level of PA and an excess TV watching time. Physical activity explains a greater amount of the variance of MetS than any other factors of lifestyle, education, sex and family history, and substantially mitigates the strong association of age and BMI with MetS.

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.

Whole-exome sequencing has become a popular technique in research and clinical settings, assisting in disease diagnosis and increasing the understanding of disease pathogenesis. In this study, we aimed to compare common enrichment capture solutions available in the market. Peripheral blood-purified DNA samples were enriched with SureSelectQXT V6 (Agilent) and various Illumina solutions: TruSeq DNA Nano, TruSeq DNA Exome, Nextera DNA Exome, and Illumina DNA Prep with Enrichment, and sequenced on a HiSeq 4000. We found that their percentage of duplicate reads was as much as 2 times higher than previously reported values for the previous HiSeq series. SureSelectQXT and Illumina DNA Prep with Enrichment showed the best average on-target coverage, which improved when off-target regions were included. At high coverage levels and in shared bases, these two solutions and TruSeq DNA Exome provided three of the best performances. With respect to the number of small variants detected, SureSelectQXT presented the lowest number of detected variants in target regions. When off-target regions were considered, its ability equalized to other solutions. Our results show SureSelectQXT and Illumina DNA Prep with Enrichment to be the best enrichment capture solutions.

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