Background Human soluble epoxide hydrolase plays a major role in cardiovascular homeostasis. Genetic variants in the EPHX2 gene among different ethnic groups are associated with cardiovascular complications, such as hypertension. However, no reports regarding the association of EPHX2 genotype with hypertension among type II diabetic (T2D) patients of Middle Eastern Jordanian origin exist. Objective The current study aimed to elucidate the association of the EPHX2 allele, genotype, and haplotype with T2D, hypertension, and parameters of lipid profile parameters among Jordanian T2D patients. Methods Ninety-three genomic DNA samples of non-diabetic controls and 97 samples from T2D patients were genotyped for EPHX2 rs4149243, rs2234914, and rs751142 genetic variants. The DNA samples were amplified using polymerase chain reaction (PCR) and then sequenced using Applied Biosystems Model (ABI3730x1). The functionality of intronic EPHX2 variants was predicted using the in silico Berkely Drosophila Genome Project software. Results We found no significant (P > 0.05) association between the EPHX2 rs4149243, rs2234914, and rs751142 allele, genotype, and haplotype and the incidence of T2D and hypertension. Additionally, no association (P > 0.05) between these EPHX2 genetic variants with the baseline total cholesterol, low- and high-density lipoproteins, and triglycerides among both non-diabetic and diabetic volunteers was found. However, we found an inter-ethnic variation (χ2 -test, p value ˂ 0.05) in the allele frequency of the EPHX2 rs4149243 and rs2234914 variants between Jordanians and other ethnic populations. Also, the in silico Berkely Drosophila Genome Project software predicted that the intronic EPHX2 rs4149243 could alter the splicing of intron 7. Conclusions It can be concluded from this study that EPHX2 rs4149243, rs2234914, and rs751142 genetic variants do not play a role in the development of T2D and hypertension among Jordanian T2D patients. Further genetic studies with larger sample sizes are needed to find out the association of other functional EPHX2 variants with cardiovascular diseases among T2D patients in Jordan.

No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients

A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: findings from the UK Biobank.

Summary Sequential conditional analysis is an important tool for identifying the unique signals in single-variant association analysis between genomic variants and various phenotypic outcomes. With large datasets, it is tedious and time-consuming to manually run the sequential steps which require the association analysis, computation of linkage disequilibrium (LD) between the variants, generation of a visualization graphic, and identification of the “top hit” to be inserted as an additional covariate for the next iteration. The Conditional Analysis Cakewalk automates this process, making it easy and fast, while only requiring user input in the initial configuration steps. Availability and Implementation The Conditional Analysis Cakewalk is implemented as a Linux shell script utilizing MMAP or PLINK and LocusZoom. Source code and documentation are available at https://github.com/jennetics/Cakewalk.

/pdf/conditional-analysis-cakewalk-28pbbqhfh4.pdf

Conditional Analysis Cakewalk


 Background Lipid metabolism disorder is closely related to diabetic nephropathy (DN), but the mechanism remains unclear. The aim of this study was to investigate the effect of high glucose on intracellular accumulation of lipids and to clarify the possible mechanism. Methods We found that in human glomerular endothelial cells (GEnCs), cholesterol could reduce cell activity, lead to abnormal lipid deposition in cells and high glucose can aggravate lipid deposition under high cholesterol load. Results CCK8 showed that soluble cholesterol could reduce GEnCs cells activity. Oil red O staining and cholesterol quantification experiment showed that the intracellular lipid deposition did not obvious after the intervention of high glucose (HG), but the intracellular lipid deposition increased under HG combined with high cholesterol (HC). The results of RT-qPCR,WB and immunofluorescence experiment showed the expression of ABCA1 in HC group increased significantly. However, compared with the HC group, the expression of ABCA1in the HG and HC group were decreased. And then we found HG affected ABCA1 up-regulation by LXRs. Based on Gene Microarray, we found that LXRs regulation of ABCA1 transcription requires the involvement of LncRNAOR13C9. Conclusions HG could enhance intracellular lipid deposition by interfering with cellular response to HC to up-regulate the expression of ABCA1, and HG blocked the expression of ABCA1 by down-regulating LXRs, and LncRNAOR13C9 also played an important role in this process. It further elucidate the pathogenesis of DN and provide a new target for the prevention and treatment of DN.

/pdf/high-glucose-aggravates-lipid-deposition-in-glomerular-3f1nxe44pz.pdf

High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells.

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Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells.