👤 Josefin A Jacobsson

Inverse associations between systemic inflammation and cholesterol ('the lipid paradox') have been reported in rheumatoid arthritis (RA) and, in established axial spondyloarthritis (axSpA), but little is known about this relationship in early axSpA, which is the focus of the present study. In the Swedish part of the SPondyloArthritis Caught Early (SPACE) cohort (patients with chronic back pain for ≥3 months, ≤2 years; age at onset <45 years), serum levels of total cholesterol (TC) and apolipoproteins ApoA1 and ApoB were measured at inclusion, together with parameters reflecting inflammatory disease activity [C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and sacroiliitis by magnetic resonance imaging (MRI) following Assessment of SpondyloArthritis international Society (ASAS) criteria]. All patients included in the analysis either had axSpA based on a high physician's level of confidence or fulfilled the ASAS criteria for axSpA. Associations between lipids/lipoproteins and inflammation were assessed using multivariable linear regression models. In the 64 patients included, there were inverse associations for CRP with TC, ApoA1, and ApoB in age-sex-adjusted models. The negative associations with CRP remained significant for TC and ApoB in multivariable models adjusted for age, sex, BASDAI, and current smoking (p = 0.048). There were no significant associations for the lipid parameters with BASDAI or inflammation on MRI of the sacroiliac joints. Inverse associations between systemic inflammation and lipids, particularly TC and ApoB, are present in early axSpA, similar to those shown for other inflammatory joint diseases. These patterns must be considered when including lipids in the evaluation of cardiovascular disease risk. Show less

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. Show less

Recent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family intracellular signaling pathways, responding to extracellular growth factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this study, we examined the association of this variant in two cohorts of children from Sweden and Greece. We examine the association of rs2241423 to BMI in a cohort of 474 Swedish children admitted for treatment of childhood obesity and 519 children matched for gender, ethnicity and socioeconomic background from the Stockholm area, as well as a cross-sectional cohort of 2308 Greek school children (Healthy Growth Study). Children were genotyped using a predesigned TaqMan polymorphism assay. Logistic regression was used to test for an association of rs2241423 to obesity in the cohort of Swedish children. Linear regression was used to test for an association of rs2241423 to BMI z-score and phenotypic measurements of body adiposity in the cohort of Greek children. Models were adjusted for age and gender. In the cohort of Greek children the model was also adjusted for stage of pubertal development. The minor allele of rs2241423, allele A, was associated with a protective effect against obesity in the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64-0.98)), and with a lower BMI z-score in the cohort of Greek children (p = 0.028, β = -0.092). No association to phenotypic measurements of body fat distribution could be observed in our study. rs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation. Show less