Distribution of APOE variants in four Northeast Indian populations

Polymorphisms in the human apolipoprotein E gene (ApoE) have been extensively studied for associations with various complex diseases. Numerous population genetic studies have reported the distribution of ApoE alleles in global populations. In this study, we present new data on the distribution of ApoE polymorphisms among four Northeast Indian populations, namely, Kachari, Rabha, Ahom, and an Indo-European caste group. Allele frequencies, Hardy-Weinberg equilibrium, genotype and phenotype probabilities were based on the two SNPs, rs7412 and rs429358. Of the APOE genotypes, derived from rs429358 and rs7412 SNPs, 3/3 and 3/4 genotypes were the most frequent in all groups and only Rabha showed higher frequency of 2/3 genotype. The Kachari population showed the highest frequency of CT genotype for SNP rs429358 and the highest frequency of allele *E4 in the Indian subcontinent, which was much higher than other study populations of eastern India

Distribution of ApoE Variants in Four Northeast Indian Populations

Polymorphisms in the human apolipoprotein E gene (ApoE) have been extensively studied for associations with various complex diseases. Numerous population genetic studies have reported the distribution of ApoE alleles in global populations. In this study, we present new data on the distribution of ApoE polymorphisms among four Northeast Indian populations, namely, Kachari, Rabha, Ahom, and an Indo-European caste group. Allele frequencies, Hardy-Weinberg equilibrium, genotype and phenotype probabilities were based on the two SNPs, rs7412 and rs429358. Of the APOE genotypes, derived from rs429358 and rs7412 SNPs, 3/3 and 3/4 genotypes were the most frequent in all groups and only Rabha showed higher frequency of 2/3 genotype. The Kachari population showed the highest frequency of CT genotype for SNP rs429358 and the highest frequency of allele *E4 in the Indian subcontinent, which was much higher than other study populations of eastern India

Distribution of ApoE Variants in Four Northeast Indian Populations

Polymorphisms in the human apolipoprotein E gene (ApoE) have been extensively studied for associations with various complex diseases. Numerous population genetic studies have reported the distribution of ApoE alleles in global populations. In this study, we present new data on the distribution of ApoE polymorphisms among four Northeast Indian populations, namely, Kachari, Rabha, Ahom, and an Indo-European caste group. Allele frequencies, Hardy-Weinberg equilibrium, genotype and phenotype probabilities were based on the two SNPs, rs7412 and rs429358. Of the APOE genotypes, derived from rs429358 and rs7412 SNPs, 3/3 and 3/4 genotypes were the most frequent in all groups and only Rabha showed higher frequency of 2/3 genotype. The Kachari population showed the highest frequency of CT genotype for SNP rs429358 and the highest frequency of allele *E4 in the Indian subcontinent, which was much higher than other study populations of eastern India

Common SNPs in FTO Gene Are Associated with Obesity Related Anthropometric Traits in an Island Population from the Eastern Adriatic Coast of Croatia

Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with "body fatness" measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of "body fatness". However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for "body fatness", two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).The current study confirmed the association of common variants of FTO gene with "body fatness" measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with "body fatness"

Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling

Abstract Background Eighty percent of patients who receive bariatric surgery are women, yet the majority of preclinical studies are in male rodents. Because sex differences drive hepatic gene expression and overall lipid metabolism, we sought to determine whether sex differences were also apparent in these endpoints in response to bariatric surgery. Methods Two cohorts of age-matched virgin male and female Long-Evans rats were placed on a high fat diet for 3 weeks and then received either Sham or vertical sleeve gastrectomy (VSG), a surgery which resects 80% of the stomach with no intestinal rearrangement. Results Each sex exhibited significantly decreased body weight due to a reduction in fat mass relative to Sham controls (p < 0.05). Microarray and follow-up qPCR on liver revealed striking sex differences in gene expression after VSG that reflected a down-regulation of hepatic lipid metabolism and an up-regulation of hepatic inflammatory pathways in females vs. males after VSG. While the males had a significant reduction in hepatic lipids after VSG, there was no reduction in females. Ad lib-fed and fasting circulating triglycerides, and postprandial chylomicron production were significantly lower in VSG relative to Sham animals of both sexes (p < 0.01). However, hepatic VLDL production, highest in sham-operated females, was significantly reduced by VSG in females but not males. Conclusions Taken together, although both males and females lose weight and improve plasma lipids, there are large-scale sex differences in hepatic gene expression and consequently hepatic lipid metabolism after VSG.http://deepblue.lib.umich.edu/bitstream/2027.42/135948/1/13293_2017_Article_126.pd

Extent of Height Variability Explained by Known Height-Associated Genetic Variants in an Isolated Population of the Adriatic Coast of Croatia

BACKGROUND: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. METHODOLOGY/PRINCIPAL FINDINGS: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. CONCLUSIONS/SIGNIFICANCE: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm.

BACKGROUND: In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant. OBJECTIVES: Our objective here was to characterize the mammary gland transcriptomes from the above study. We hypothesized that proinflammatory gene expression would be attenuated in the increased DHA group compared with the standard DHA group. METHODS: In the original trial, mothers delivering at&nbsp;&lt;29&nbsp;wk gestation at the University of Cincinnati Medical Center and intending to express their milk were randomly assigned to supplementation with 200&nbsp;mg/d DHA (standard group: STD) or 1000&nbsp;mg/d DHA (experimental group: EXP) within 7 d of delivery. Here, we conducted RNA-seq transcriptome analysis of n&nbsp;=&nbsp;5 EXP and n&nbsp;=&nbsp;4 STD extracellular mammary mRNA samples extracted from the fat layer of milk samples obtained 4 wk postenrollment. Transcripts were assessed for differential expression (false discovery rate adjusted P value&nbsp;&lt;0.05)&nbsp;and clustering between EXP compared with STD groups. Ontological analysis of all differentially expressed genes (DEGs) was performed with Toppcluster. RESULTS: There were 409 DEGs. We observed 5 main groups of biological processes that were upregulated, including those associated with improved immune regulation and management of oxidative stress; and 3 main groups of biological processes that were downregulated, including 1 associated with immune dysregulation. For example, we observed upregulation of inflammation-inhibiting genes including NFKB inhibitor alpha (NFKBIA; fold-change (FC), adjusted P value: FC = 1.70, P&nbsp;=&nbsp;0.007) and interleukin-18 binding protein (IL18BP: FC = 2.2, adjusted P&nbsp;=&nbsp;0.02); and downregulation of proinflammatory genes including interleukin 7 receptor (IL7R: FC = -1.9, adjusted P&nbsp;=&nbsp;0.02) and interleukin 1 receptor like 1 (IL1RL1: FC = -13.0, adjusted P&nbsp;=&nbsp;0.02). CONCLUSIONS: Increased DHA supplementation during lactation can modulate the expression of inflammation-related genes within the mammary gland. This might translate to milk composition with a more optimal inflammasome profile. Future research with a larger clinical trial and greater interrogation of clinical outcomes is warranted

The Synthetic Opioid Fentanyl Increases HIV Replication and Chemokine Co-Receptor Expression in Lymphocyte Cell Lines

Background: In the United States, the illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis. Synthetic opioids are known to enhance viral replication and to suppress immunologic responses, but their effects on HIV pathogenesis remain unclear. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types. Methods: TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at varying concentrations. Expression levels of the CXCR4 and CCR5 chemokine receptors and HIV p24 antigen were quantified with ELISA. HIV proviral DNA was quantified using SYBR RT-PCR. Cell viability was detected with the MTT assay. RNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Results: Fentanyl enhanced expression of both chemokine receptor levels in a dose-dependent manner in HIV-susceptible and infected cell lines. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral/interferon response, chemokine signaling, and NFκB signaling were differentially regulated. Conclusions: Synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression. Increased virus levels suggest that opioid use may increase the likelihood of transmission and accelerate disease progression