Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.

Protease inhibitors (PIs) are associated with an incidence of lipodystrophy among people living with HIV(PLHIV). Lipodystrophiesare characterised by the loss of adipose tissue. Evidence suggests that a patient's lipodystrophy phenotype is influenced by genetic mutation, age, gender, and environmental and genetic factors, such as single-nucleotide variants (SNVs). Pathogenic variants are considered to cause a more significant loss of adipose tissue compared to non-pathogenic. Lipid metabolising enzymes and transporter genes have a role in regulating lipoprotein metabolism and have been associated with lipodystrophy in HIV-infected patients (LDHIV). The long-term effect of the lipodystrophy syndrome is related to cardiovascular diseases (CVDs). Hence, we determined the SNVs of lipid metabolising enzymes and transporter genes in a total of 48 patient samples, of which 24 were with and 24 were without HIV-associated lipodystrophy (HIVLD) using next-generation sequencing. A panel of lipid metabolism, transport and elimination genes were sequenced. Three novel heterozygous non-synonymous variants at exon 8 (c.C1400A:p.S467Y, c.G1385A:p.G462E, and c.T1339C:p.S447P) in the ABCB6 gene were identified in patients with lipodystrophy. One homozygous non-synonymous SNV (exon5:c.T358C:p.S120P) in the GRN gene was identified in patients with lipodystrophy. One novelstop-gain SNV (exon5:c.C373T:p.Q125X) was found in the GRN gene among patients without lipodystrophy. Patients without lipodystrophy had one homozygous non-synonymous SNV (exon9:c.G1462T:p.G488C) in the ABCB6 gene. Our findings suggest that novel heterozygous non-synonymous variants in the ABCB6 gene may contribute to defective protein production, potentially intensifying the severity of lipodystrophy. Additionally, identifying a stop-gain SNV in the GRN gene among patients without lipodystrophy implies a potential role in the development of HIVLD.

Comparative analysis of MTP -493G/T and ABCG2 34G/A polymorphisms and theirs expression in HIV-associated lipodystrophy patients.

HIV-associated lipodystrophy (HIVLD) is a metabolic condition with an irregularity in the production of lipoprotein particles, and its occurrence varies among HIV-infected patients. MTP and ABCG2 genes have a role in the transport of lipoproteins. The polymorphisms of MTP -493G/T and ABCG2 34G/A affect its expression and influence the secretion and transportation of lipoproteins. Hence, we investigated the MTP -493G/T and ABCG2 34G/A polymorphisms in 187 HIV-infected patients (64 with HIVLD and 123 without HIVLD) along with 139 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism and expression analysis using real-time PCR. ABCG2 34A allele showed an insignificantly reduced risk of LDHIV severity [P = 0.07, odds ratio (OR) = 0.55]. MTP -493T allele exhibited a non-significantly reduced risk for the development of dyslipidemia (P = 0.08, OR = 0.71). In patients with HIVLD, the ABCG2 34GA genotype was linked with impaired low-density lipoprotein levels and showed a reduced risk for LDHIV severity (P = 0.04, OR = 0.17). In patients without HIVLD, the ABCG2 34GA genotype was associated with impaired triglyceride levels with marginal significance and showed an increased risk for the development of dyslipidemia (P = 0.07, OR = 2.76). The expression level of MTP gene was 1.22-fold decreased in patients without HIVLD compared with that in patients with HIVLD. ABCG2 gene was upregulated 2.16-fold in patients with HIVLD than in patients without HIVLD. In conclusion, MTP -493C/T polymorphism influences the expression level of MTP in patients without HIVLD. Individuals without HIVLD having ABCG2 34GA genotype with impaired triglyceride levels may facilitate dyslipidemia risk.

Assessment of determining factors for severity of NeoCOVIDiabetes in India: A pan India multicentric retrospective study.

BACKGROUND AND AIMS: There is a bidirectional relationship between COVID-19 and diabetes. The primary objective of this study was to estimate the prevalence of patients newly detected to have diabetes (NDD) who recovered from COVID-19 in India whilst comparing NDD with patients without diabetes (ND) and those who have known to have diabetes (KD) in terms of glycemic status pre- and post-COVID with disease severity. MATERIALS & METHODOLOGY: There were 2212 participants enrolled from 15 sites, with 1630 active participants after the respective execution of selection criteria. Data collection was done using a specialized Case Record Form (CRF). Planned statistical analysis and descriptive statistics were concluded for significance between patient groups on various parameters. RESULT: The differences in age between the study groups were statistically significant. The average blood glucose at COVID-19 onset was significantly higher in KD than in NDD. Significantly more proportion of NDD (83%) had been hospitalized for COVID management when compared to KD (45%) and ND (55%). The NDD group received higher doses of steroids than the other two groups. On average, patients in the NDD group who received at least one vaccination (one dose or two doses) had a higher High-Resolution Computed Tomography (HRCT) score. Patients who had not been vaccinated in ND and KD groups experienced a higher HRCT score. CONCLUSION: Prospective metabolism studies in post-acute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

Membrane-derived oligosaccharides (MDOs) are essential for sodium dodecyl sulfate resistance in Escherichia coli.

We studied the role of membrane-derived oligosaccharides (MDOs) in sodium dodecyl sulfate (SDS) resistance by Escherichia coli. MDOs are also known as osmoregulated periplasmic glucans. Wild-type E. coli MC4100 grew in the presence of 10% SDS whereas isogenic mdoA and mdoB mutants could not grow above 0.5% SDS. Similarly, E. coli DF214, a mutant (pgi, zwf) unable to grow on glucose, exhibited conditional sensitivity to SDS in that it grew in gluconate and glucose or galactose but not in gluconate and mannose or sorbose. DF214 requires both gluconate and glucose/galactose because the gluconate is used for energy production, while glucose/galactose is used for MDO synthesis. Finally, the fate of E. coli cells subjected to SDS shock either during growth or when used as an inoculum is dependent on the presence or absence of sufficient MDOs. In both cases, cells grown under high-osmolarity (low-MDO) conditions were rapidly lysed by 5% SDS. Based on findings from a wild-type E. coli (MC4100), two mdo mutants and strain DF214 we conclude that MDOs are required for SDS resistance.