Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

n-3 Polyunsaturated fatty acids (n-3 PUFAs) have anti-obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genome-wide association studies (GWAS) have identified genetic variants associated with body mass index (BMI); however, the extent to which these variants influence adiposity through interactions with n-3 PUFAs remains unknown. We evaluated 10 highly replicated obesity GWAS single nucleotide polymorphisms (SNPs) for individual and cumulative associations with adiposity phenotypes in a cross-sectional sample of Yup’ik people (n = 1,073) and evaluated whether genetic associations with obesity were modulated by n-3 PUFA intake. A genetic risk score (GRS) was calculated by adding the BMI-increasing alleles across all 10 SNPs. Dietary intake of n-3 PUFAs was estimated using nitrogen stable isotope ratio (δ¹⁵N) of red blood cells, and genotype–phenotype analyses were tested in linear models accounting for familial correlations. GRS was positively associated with BMI (p = 0.012), PBF (p = 0.022), ThC (p = 0.025), and waist circumference (p = 0.038). The variance in adiposity phenotypes explained by the GRS included BMI (0.7 %), PBF (0.3 %), ThC (0.7 %), and WC (0.5 %). GRS interactions with n-3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (~1–2 %), relative to GRS associations alone. Obesity GWAS SNPs contribute to adiposity in this study population of Yup’ik people and interactions with n-3 PUFA intake potentiated the risk of fat accumulation among individuals with high obesity GRS. These data suggest the anti-obesity effects of n-3 PUFAs among Yup’ik people may, in part, be dependent upon an individual’s genetic predisposition to obesity.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-013-0340-z) contains supplementary material, which is available to authorized users.     

Proteome analysis of the left ventricle in the vitamin D₃ and nicotine-induced rat vascular calcification model

Vitamin D? and nicotine (VDN) serve as an animal model of arterial calcification. The vascular calcification induced by the VDN model is always accompanied by compensatory left ventricular (LV) hypertrophy and impaired cardiac performance. To determine the possible mechanisms that are responsible for the effects of VDN on the LV, a 2-DE based proteomics approach was used to evaluate the changes in protein expression of the left ventricle in VDN rats, to our knowledge, for the first time. We identified sixteen proteins that were markedly altered and involved in mitochondrial function, heat shock protein activity, myocyte cytoskeleton composition and enzyme activity for energy metabolism. We describe, for the first time, a novel pathway (NDPK) that is involved in LV hypertrophy and enzyme activities of three of the sixteen clinical identified proteins: lactate dehydrogenase (LDH), SOD [Mn] and GST.     

Consumption of non–cow’s milk beverages and serum vitamin D levels in early childhood

Background:

Vitamin D fortification of non–cow’s milk beverages is voluntary in North America. The effect of consuming non–cow’s milk beverages on serum 25-hydroxyvitamin D levels in children is unclear. We studied the association between non–cow’s milk consumption and 25-hydroxyvitamin D levels in healthy preschool-aged children. We also explored whether cow’s milk consumption modified this association and analyzed the association between daily non–cow’s milk and cow’s milk consumption.

Methods:

In this cross-sectional study, we recruited children 1–6 years of age attending routinely scheduled well-child visits. Survey responses, and anthropometric and laboratory measurements were collected. The association between non–cow’s milk consumption and 25-hydroxyvitamin D levels was tested using multiple linear regression and logistic regression. Cow’s milk consumption was explored as an effect modifier using an interaction term. The association between daily intake of non–cow’s milk and cow’s milk was explored using multiple linear regression.

Results:

A total of 2831 children were included. The interaction between non–cow’s milk and cow’s milk consumption was statistically significant (p = 0.03). Drinking non–cow’s milk beverages was associated with a 4.2-nmol/L decrease in 25-hydroxyvitamin D level per 250-mL cup consumed among children who also drank cow’s milk (p = 0.008). Children who drank only non–cow’s milk were at higher risk of having a 25-hydroxyvitamin D level below 50 nmol/L than children who drank only cow’s milk (odds ratio 2.7, 95% confidence interval 1.6 to 4.7).

Interpretation:

Consumption of non–cow’s milk beverages was associated with decreased serum 25-hydroxyvitamin D levels in early childhood. This association was modified by cow’s milk consumption, which suggests a trade-off between consumption of cow’s milk fortified with higher levels of vitamin D and non–cow’s milk with lower vitamin D content.Goat’s milk and plant-based milk alternatives made from soy, rice, almonds, coconut, hemp, flax or oats (herein called “non–cow’s milk”) are increasingly available on supermarket shelves. Many consumers may be switching from cow’s milk to these beverages.^1–3 Parents may choose non–cow’s milk beverages for their children because of perceived health benefits. However, it is unclear whether they offer health advantages over cow’s milk or, alternatively, whether they increase the risk of nutritional inadequacy.In the United States and Canada, cow’s milk products are required to contain about 40 IU of vitamin D per 100 mL, making it the major dietary source of vitamin D for children.^4–8 The only other food source with mandatory vitamin D fortification in Canada is margarine, which is required to contain 53 IU per 10 mL (10 g).⁵ Fortification of non–cow’s milk beverages with vitamin D is also possible, but it is voluntary in both countries. Furthermore, there is little regulation on the vitamin D content even if such beverages are fortified.^5,6,9We conducted a study to test the association between total daily consumption of non–cow’s milk and serum 25-hydroxyvitamin D levels in a population of healthy urban preschool-aged children attending routinely scheduled well-child visits. We hypothesized that vitamin D stores would be lower in children who consume non–cow’s milk. The secondary objectives were to explore how consumption of cow’s milk might modify this association and to study the association between daily intake of non–cow’s milk and cow’s milk.     

Use of the STR loci D18S53, D18S59, and D18S488 in the diagnosis of Edwards’ syndrome

The aim of this study was to investigate the feasibility of using short tandem repeats (STRs) to diagnose Edwards’ syndrome (ES). Quantitative fluorescence polymerase chain reaction (QF-PCR) was performed to amplify STR loci on chromosome 18, specifically D18S53, D18S59, and D18S488. The amplified products were subjected to a fluorescence signal analysis and their application to ES diagnosis was examined. Among the 807 cases that showed normal results in the karyotype analysis, 793 showed one or two fluorescence bands with a fluorescence intensity ratio of 1:1, and 14 cases showed 3 bands, which were false-positive results. ES was diagnosed in 9 samples. The sensitivities of D18S53, D18S59, and D18S488 for the diagnosis of ES were 77.78, 44.44, and 55.56 % and the specificities were 96.16, 96.03, and 96.28 %, respectively. The combined sensitivity of the three loci for diagnosing DS was 100 % (9/9), with a specificity of 98.27 % (793/807). QF-PCR amplification of STR loci had high sensitivity, strong specificity, and was simple and rapid. Thus, it might have wide clinical applications, and could be an ideal tool for large-scale genetic and prenatal diagnosis of ES.     

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

Previously, we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24–27 (LOD 2.26). To comprehensively evaluate this region, we performed a two-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM end-stage renal disease (ESRD) subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P < 0.05) in one or more of tests of association: allelic (n = 33), dominant (n = 36), additive (n = 29), or recessive (n = 34) genotypic models, and 2- (n = 47) and 3-SNP (n = 43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP “risk” haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes, including suggestive associations in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24–27 in AA. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Stimulation of cellular autophagy by parathyroid hormone and cyclic adenosine 3′,5′: Monophosphate in isolated tubular fragments from the rat’s kidney cortex

Tubular fragments isolated from the cortex of the rat's kidney were qualitatively and quantitatively investigated with the electron microscope. The tubules frequently burst open and became "inverted" in such a way that the rarefied brush border now formed the outer circumference. By morphometry a decrease of the average cell volume in the proximal tubular fragments was ascertained. This was mostly caused by a loss of cytoplasmic ground substance, endoplasmic reticulum and ribosomes. Cytoplasmic herniations of the basal surface, filled with free ribosomes, suggested a partial shedding of the protein synthesizing apparatus. The number of autophagic vacuoles (AV) per unit area of cytoplasm was determined in proximal tubular fragments. After isolation alone, without further incubation, the number of AV was as low as the number found in an earlier study in proximal tubular cells in situ during the diurnal minimum. After control incubation the number of AV increased to about the mean value of the AV found in cells in situ during the whole diurnal cycle. By comparison with the control incubation the number of AV increased by a factor of 1.6 to 1.7, if cyclic adenosine 3',5': monophosphate (cyclic AMP) or parathyroid hormone (PTH) were added to the incubation-medium; it now reached about the number of AV found in situ during the diurnal maximum. The increase in the number of AV paralleled that of the production of ammonia and glucose from endogenous sources under the influence of cyclic AMP and PTH. This suggests that the breakdown of cytoplasmic components by cellular autophagy could be functionally related to gluconeogenesis. A quantitative comparison between the measured production of ammonia and glucose indicates, however, that in the system of isolated tubular fragments there may exist other mechanisms of degradation, and of the provision of substrates for gluconeogenesis, than cellular autophagy only.     

A class of novel Schiff’s bases: Synthesis,therapeutic action for chronic pain,anti-inflammation and 3D QSAR analysis

To discover analgesics for treating chronic pain 17 novel Schiff’s bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff’s bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff’s bases exhibited desirable anti-inflammation. Thus the present Schiff’s bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff’s bases on the analgesic activity was explained with 3D QSAR.     

Determination of fatty acid profiles,cholesterol and D,E, K vitamin’s content in Astacus leptodactylus caught from wild prior to reproduction period

In this study, fatty acids compositions, fat-soluble vitamins (D, E, and K) and cholesterol in the gonads, hepatopancreas, and abdomen muscle of male and female Astacus leptodactylus caught from wild were determined in their prior of reproduction period. The results showed that in female A. leptodactylus, compared with hepatopancreas, the ovaries contained a significantly high level of C16:0, C16:1n-7, C18:1n-9, C22:6n-3, the ratio of n-3 to n-6 (p < 0.05). In females, the values of δ-tocopherol, α-tocopherol, K₂ and D₂ vitamins, and cholesterol obtained in ovaries were significantly higher than those of obtained in abdomen muscle and hepatopancreas (p < 0.05). In male A. leptodactylus δ-tocopherol was found to be 1.91 μg/g in testes, which is significantly higher than that of abdomen muscle, hepatopancreas, and vasa deferentia (p < 0.05). In conclusion, the findings of present study are especially constructive for both crayfish biologists and farmers for preparing broodstock diets for crayfish at reproduction units.