Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ≤ 7.2 × 10−16), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10−9) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10−7). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ≤ 1.6 × 10−9). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C–G haplotype in both CLHNS mothers (P = 1.8 × 10−25) and offspring (P = 8.7 × 10−32). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1–ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos.

IntroductionNearly 90% of all deaths in the Republic of Moldova are caused by non-communicable diseases, the majority of which (55%) are caused by cardiovascular diseases (CVD). In addition to reducing premature mortality from CVD, it is estimated that strengthening primary healthcare could cut the number of hypertension-related hospital admissions and diabetes-related hospitalisations in half. The aim of this evaluation is to determine the feasibility of implementing and evaluating essential interventions for the prevention of CVD in primary healthcare in the Republic of Moldova, with a view towards national scale-up.Methods and analysisA national steering group including international experts will be convened to adapt WHO Package of Essential NCD Intervention from Primary Healthcare in Low Resource Settings protocols 1 and 2 to the health system of the Republic of Moldova, develop and conduct training of primary healthcare workers and test a core set of indicators to monitor the quality of care and change in clinical practice. To evaluate the impact of this pilot implementation, a pragmatic, sequential mixed methods explanatory design, composed of quantitative and qualitative strands of equal weight, will be used. Twenty primary healthcare centres will be selected and randomised to the training and implementation arm (n=10) and the usual care arm (n=10). At baseline and 12 months follow-up, a standardised data collection form will be piloted to extract data directly from patient paper records in order to estimate the change in clinical practice. Semi-structured interviews and interclinic peer workshops will be conducted at 12 months follow-up, and qualitative data collected from these formats will be analysed thematically for explanatory themes that relate to the quantitative findings.Ethics and disseminationEthical review and approval has been obtained. Findings of the evaluation will be shared in a project report to key stakeholders, presented back to participants and written into a manuscript for an open access peer-reviewed scientific journal.

C-reactive protein (CRP) is a component of non-specific immune defense and is a reliable marker of low-grade inflammation involved in obesity, type 2 diabetes and cardiovascular disease. Genome-wide association studies (GWAS) in middle-aged and elderly populations, predominantly of European descent, demonstrated associations of CRP levels with SNPs at several loci. To examine whether the variants identified are replicated in Filipino young adults, we applied Tobit regression models to study the association of plasma CRP with 12 SNPs at seven loci in a cohort of 1,691 Filipino young adults (aged 21.5 ± 0.3 years) from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). SNPs in or near CRP (P = 3.2 × 10-11), HNF1A, IL6R, APOE-APOC1 and LEPR showed significant associations (P < 0.05) and together explained 4.8% of the total variation in CRP. Modest interactions were observed between LEPR rs1892534 and waist circumference (uncorrected Pinteraction = 0.020) and between APOE rs769449 and pathogen exposure (uncorrected Pinteraction = 0.0073) in models predicting CRP. Our results demonstrated that variants in several loci are significantly associated with plasma CRP in Filipino young adults, suggesting shared genetic influences on circulating CRP across populations and age groups.

Background The aim of this study is to determine the feasibility of implementing and evaluating the World Health Organization Package of Essential Non-communicable Disease Interventions (WHO PEN) approach in primary healthcare in the Republic of Moldova. Methods According to our published a priori methods, 20 primary care clinics were randomized to 10 intervention and 10 control clinics. The intervention consisted of implementation of adapted WHO PEN guidelines and structured training for health workers; the control clinics continued with usual care. Data were gathered from paper-based patient records in July 2017 and August 2018 resulting in a total of 1174 and 995 patients in intervention and control clinics at baseline and 1329 and 1256 at follow-up. Pre-defined indicators describing assessment of risk factors and total cardiovascular risk, prescribing medications and treatment outcomes were calculated. Differences between baseline and follow-up as well as between intervention and control clinics were calculated using logistic and linear regression models and by assessing interaction effects. Results Improvements were seen in recording smoking status, activity to measure HbA1c among diabetes patients and achieving control in hypertension treatment. Improvement was also seen in identification of patients with hypertension or diabetes. Less improvement or even deterioration was seen in assessing total risk or prescribing statins for high-risk patients. Conclusions It is feasible to evaluate the quality and management of patients with non-communicable diseases in low-resource settings from routine data. Modest improvements in risk factor identification and management can be achieved in a relatively short period of time.