👤 Jeanette Wahlberg

C-peptide has a complex role in human physiology, but its effects are not fully understood. Studies have shown a protective impact against diabetic complications, but also that C-peptide levels associate with cardiovascular events. Among the many applications to assess cardiovascular risk, circulating lipids are widely used, and one of the strongest biomarkers is apolipoprotein B. The aim of this investigation was to study the association of C-peptide with markers of metabolic, inflammatory, or cardiovascular alterations in a limited group of healthy individuals. Body mass index (BMI), lipids, and other plasma markers were studied in 28 consecutive healthy individuals within the age of 30-50 years. The results showed significant positive correlations between C-peptide and BMI (r = 0.498; p = 0.007); hsCRP (r = 0.530; p = 0.004); triglycerides (r = 0.530; p = 0.005); cholesterol (r = 0.507; p = 0.006), LDL-cholesterol (r = 0.550; p = 0.002), LDL/HDL ratio (r = 0.460; p = 0.014); apoB (r = 0.622; p < 0.001), apoB/apoA1 ratio (r = 0.563; p = 0.002); and non-HDL cholesterol (r = 0.566; p = 0.002). According to BMI values, 16 of the 28 individuals were overweight (BMI >25.0 kg/m Show less

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population. Show less

Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P = 0.03; TC compared with CC, β = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P = 0.04). In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations. Show less

Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression. To investigate whether PFAS exposure is associated with altered microRNA expression in serum. We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA). Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα). PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects. Show less

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment. Show less