Summary Background Obesity is a major health problem that is determined by interactions between lifestyle and environmental and genetic factors. Although associations between several genetic variants ...and body-mass index (BMI) have been identified, little is known about epigenetic changes related to BMI. We undertook a genome-wide analysis of methylation at CpG sites in relation to BMI. Methods 479 individuals of European origin recruited by the Cardiogenics Consortium formed our discovery cohort. We typed their whole-blood DNA with the Infinium HumanMethylation450 array. After quality control, methylation levels were tested for association with BMI. Methylation sites showing an association with BMI at a false discovery rate q value of 0·05 or less were taken forward for replication in a cohort of 339 unrelated white patients of northern European origin from the MARTHA cohort. Sites that remained significant in this primary replication cohort were tested in a second replication cohort of 1789 white patients of European origin from the KORA cohort. We examined whether methylation levels at identified sites also showed an association with BMI in DNA from adipose tissue (n=635) and skin (n=395) obtained from white female individuals participating in the MuTHER study. Finally, we examined the association of methylation at BMI-associated sites with genetic variants and with gene expression. Findings 20 individuals from the discovery cohort were excluded from analyses after quality-control checks, leaving 459 participants. After adjustment for covariates, we identified an association (q value ≤0·05) between methylation at five probes across three different genes and BMI. The associations with three of these probes—cg22891070, cg27146050, and cg16672562, all of which are in intron 1 of HIF3A —were confirmed in both the primary and second replication cohorts. For every 0·1 increase in methylation β value at cg22891070, BMI was 3·6% (95% CI 2·4–4·9) higher in the discovery cohort, 2·7% (1·2–4·2) higher in the primary replication cohort, and 0·8% (0·2–1·4) higher in the second replication cohort. For the MuTHER cohort, methylation at cg22891070 was associated with BMI in adipose tissue (p=1·72 × 10−5 ) but not in skin (p=0·882). We observed a significant inverse correlation (p=0·005) between methylation at cg22891070 and expression of one HIF3A gene-expression probe in adipose tissue. Two single nucleotide polymorphisms—rs8102595 and rs3826795—had independent associations with methylation at cg22891070 in all cohorts. However, these single nucleotide polymorphisms were not significantly associated with BMI. Interpretation Increased BMI in adults of European origin is associated with increased methylation at the HIF3A locus in blood cells and in adipose tissue. Our findings suggest that perturbation of hypoxia inducible transcription factor pathways could have an important role in the response to increased weight in people. Funding The European Commission, National Institute for Health Research, British Heart Foundation, and Wellcome Trust.
It is unclear if immunosuppression increases the likelihood of malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and whether adverse renal outcomes in kidney ...transplant recipients with MGUS are more frequent.
We performed a retrospective cohort study of kidney transplant recipients at the Centre Hospitalier de l'Université de Montréal between 2000 and 2016.
Among 755 study participants, 13 (1.7%) were found to have MGUS before transplant. Two evolved to smoldering multiple myeloma and 2 presented paraprotein-induced allograft injury from light chain deposition disease. Forty-six patients developed posttransplant MGUS (2.5% 5-y cumulative incidence) of which 1 progressed to multiple myeloma and 1 experienced kidney allograft loss from light chain deposition disease. None of the patients with a malignant transformation or paraprotein-induced renal disease after transplantation had had a systematic workup before transplantation to exclude hematologic malignancies and paraprotein-related kidney injury. Nine posttransplant MGUS (21%) were transient. Multivariable analysis revealed that age at transplant (hazard ratio 1.05 per 1-y increase, 95% confidence intervals, 1.02-1.08) and prior cytomegalovirus infection (hazard ratio 2.22, 95% confidence intervals, 1.07-4.58) were associated with the development of MGUS after transplantation. Of 7 posttransplant lymphoproliferative disorders, none were preceded by MGUS.
Our results suggest that the identification of MGUS in a transplant candidate should lead to further investigations to exclude a plasma cell neoplasm and monoclonal gammopathy of renal significance before transplantation. MGUS arising after transplantation appears to carry a favorable evolution.
To describe the timed manual wheelchair slalom test (MWST) and to quantify its test-retest reliability, standard error of measurement, and minimum detectable change (MDC).
Repeated-measures design.
...Pathokinesiology laboratory.
Manual wheelchair users (N=15) with spinal cord injury (SCI) (vertebral levels, C6 to T12; American Spinal Injury Association Impairment Scale: A, B, or C) participated in this study. Participants were 40.7±12.6 years of age, measured 1.77±.08m in height, weighed 79.6±23.9kg, and had been using a manual wheelchair as their primary mode of mobility for 5.9±7.5 years.
Participants propelled their own wheelchair at a self-selected maximum velocity along a slalom trajectory (linear length, 18m) defined by 7 cones aligned in a straight line and set 3m, 2m, and 1m apart from one another. Three trials (T=3) of the MWST were performed on 2 separate visits (V=2) 6.3±5.4 days apart. The generalizability theory was used to determine the reliability, standard error of measurement, and MDC and to propose testing protocols for the MWST.
The time needed to complete the MWST expressed in seconds.
All participants successfully completed the MWST. No adverse effect was reported. The time required to complete the MWST at visits 1 and 2 was 16.8±4.4 and 16.5±4.3 seconds, respectively. The reliability coefficient (φ=.981) and accuracy (standard error of measurement=3.47%, MDC=8.097%) were high when the time required for a participant to perform 3 MWST trials during a single visit (T=3, V=1) was averaged.
The timed MWST is a safe, reliable, and accurate performance-based outcome measure that can be administered easily and quickly in individuals with SCI who rely on a manually propelled wheelchair for mobility.
Background A decrease in seasonal influenza vaccine uptake was observed after the influenza A(H1N1) pandemic in 2009. The goal of our study was to assess seasonal influenza vaccine uptake in ...2011-2012, 2 years after the influenza A(H1N1) pandemic mass immunization campaign and to identify the main reasons for having or not having received the vaccine. Methods A telephone survey using random-digit dialing methodology was conducted. Case-weights were assigned to adjust for disproportionate sampling and for nonresponse bias. Descriptive statistics were generated for all variables. Results Seasonal influenza vaccine uptake was 57% among adults aged ≥60 years, 35% among adults with chronic medical conditions, and 44% among health care workers. The main reasons given for having been vaccinated were to be protected from influenza and a high perceived susceptibility to influenza, whereas low perceived susceptibility to influenza and low perceived severity of influenza were the main reasons for not having been vaccinated. Conclusions An increase in seasonal influenza vaccine uptake was observed 2 years after the influenza A(H1N1) pandemic. However, vaccine coverage is still below the target level of 80%. More efforts are needed to develop effective strategies to increase seasonal influenza vaccine uptake.
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