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Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD). However, there are several contradictions in these previous works and no consistent HLA associations with ESRD itself have been identified. Most of these works have several limitations, for instance, the population size was too small, or only limited HLA loci were studied. The presented work aims to revisit the association between ESRD and HLA antigens while taking in to account the previously overlooked limitations. Here, we compared the HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n=497) and controls (n=672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD among which HLA-A*3 –HLA-A*26 combination showed the highest strength of association (OR= 4.488, P≤ 0.05) with ESRD. However, the age of ESRD onset was not affected by HLA allele combinations at different loci. Most of the previous works have studied the association of HLA with ESRD in homogeneous ethnic groups and have interpreted their data accordingly. Here, we also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. This analysis showed that at least for certain alleles, the association of HLA to ESRD can be similar in different ethnic groups. For instance, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4 all showed significant positive associations with ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.
Cancer cell lipid class homeostasis is altered under nutrient-deprivation but stable under hypoxia
(2018)
Under oxygen/nutrient deprivation cancer cells modify the Balance between fatty acid (FA) synthesis and uptake, which alters the levels of individual triglyceride or phospholipid sub-species. These modifications may affect survival and drug-uptake in cancer cells. Here, we aimed to attain a more holistic overview of the lipidomic profiles of cancer cells under stress and assess the changes in Major lipid-classes. First, expressions of markers of FA synthesis/uptake in cancer cells were assessed and found to be differentially regulated under metabolic stress. Next, we performed a broad lipidomics assay, comprising 244 lipids from six major classes, which allowed us to investigate robust stress induced changes in median levels of different lipid classes -additionally stratified by fatty acid side chain saturation status. The lipidomic profiles of cancer cells were predominantly affected by nutrient-deprivation. Neutral lipid compositions were markedly modified under serum-deprivation and, strikingly, the cellular level of triglyceride subspecies decreased with increasing number of double bonds in their fatty acyl chains. In contrast, cancer cells maintained lipid class homeostasis under hypoxic stress. We conclude that although the levels of individual lipid moieties alter under hypoxia, the robust averages of broader lipid class remain unchanged.