Intronic Variants of the Angiotensin-Converting Enzyme 2 Gene Modulate Plasma ACE2 Levels and Possibly Confer Protection against Severe COVID-19.

Membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor acts as the entry point for the novel coronavirus, SARS-CoV-2. Polymorphisms in the ACE2 gene may alter viral binding, regulate the expression of ACE2, and thus, affect disease severity. In this study, 68 COVID-19 patients with varying degrees of severity and 40 healthy controls were enrolled. The genetic landscape of the ACE2 gene was explored by whole exome sequencing of 29 individuals, and specific regions of ACE2 were analyzed for the rest of the participants via PCR, followed by barcode-tagged sequencing. The mean soluble ACE2 level in the plasma of healthy controls and patients did not vary significantly but was higher in the patient group (3.77 ± 1.55 ng/mL vs. 3.94 ± 1.42 ng/mL). Analysis of exon 1, exon 2, and exon 8 of the ACE2 gene revealed that these regions are highly conserved in our population. Investigation of exon 11 and its flanking intronic region revealed that deletions in a stretch of 18T nucleotides in the noncoding region significantly decrease ACE2 levels in plasma, as individuals harboring wild-type variants had higher plasma ACE2 levels compared to those harboring T1del, T2del, and T3del variants. However, the intronic variants were not found to be significantly associated with disease severity.

Reappraisal of screening strategy in hepatitis B surface antigen-negative blood donors: Correlation with hepatitis B virus-DNA quantification.

BACKGROUND: In spite of screening for hepatitis B surface antigen (HBsAg), transfusion-associated hepatitis B virus (TAHBV) infection remains a serious public health problem due to transmission of HBV in window period and occult HBV infection. To avoid TAHBV infection, some health-care facilities have started Hepatitis B core antibody test along with HBsAg, but this leads to a lot of potential donor rejection who are not HBV infected. Our aim is to find a new protocol of donor screening to prevent TAHBV without compromising blood availability. MATERIALS AND METHODS: A total of 88 HBsAg-negative anti-HBc total positive blood donors were included in this study. All samples were also tested for anti-HBs by enzyme immunoassay and for the presence of HBV-DNA viral load by real-time polymerase chain reaction. RESULTS: A total of 88 HBsAg negative and anti-HBc, total positive blood donors were tested for anti-HBs and HBV-DNA (Qn.). Among them, 76 donors (86.4%) (males 73 and females 3) were found to be positive for anti-HBs, while rest 12 (13.6%) showed no detectable antibody against HBsAg. HBV-DNA was found to be positive in 4 (7.7%) donor samples among 52 (60%) who have anti-HBs level <100 mIU/ml, while 36 (40%) donor samples were found to have >100 mIU/ml anti-HBs antibody with no detectable HBV-DNA. CONCLUSION: HBV-DNA should be implemented as a screening test of the blood donors to prevent TAHBV infection without potential donor rejection.

Evaluation of D-loop hypervariable region I variations, haplogroups and copy number of mitochondrial DNA in Bangladeshi population with type 2 diabetes.

The profound impact of mitochondrion in cellular metabolism has been well documented. Since type 2 diabetes (T2D) is a metabolic disorder, mitochondrial dysfunction is intricately linked with the disease pathogenesis. Mitochondrial DNA (mtDNA) variants are involved with functional dysfunction of mitochondrion and play a pivotal role in the susceptibility to T2D. In this study, we opted to find the association of mtDNA variants within the D-loop hypervariable region I (HVI), haplogroups and mtDNA copy number with T2D in Bangladeshi population. A total of 300 unrelated Bangladeshi individuals (150 healthy and 150 patients with T2D) were recruited in the present study, their HVI regions were amplified and sequenced using Sanger chemistry. Haplogrep2 and Phylotree17 tools were employed to determine the haplogroups. MtDNA copy number was measured using primers of mitochondrial tRNALeu (UUR) gene and nuclear ß2-microglobulin gene. Variants G16048A (OR:0.12, p = 0.04) and G16129A (OR: 0.42, p = 0.007) were found to confer protective role against T2D according to logistic regression analysis. However along with G16129A, two new variants C16294T and T16325C demonstrated protective role against T2D when age and gender were adjusted. Haplogroups A and H showed significant association with the risk of T2D after adjustments out of total 19 major haplogroups identified. The mtDNA copy numbers were stratified into 4 groups according to the quartiles (groups with lower, medium, upper and higher mtDNA copy numbers were respectively designated as LCN, MCN, UCN and HCN). Patients with T2D had significantly lower mtDNA copy number compared to their healthy counterparts in HCN group. Moreover, six mtDNA variants were significantly associated with mtDNA copy number in the participants. Thus, our study confers that certain haplogroups and novel variants of mtDNA are significantly associated with T2D while decreased mtDNA copy number (though not significant) has been observed in patients with T2D. However, largescale studies are warranted to establish association of novel variants and haplogroup with type 2 diabetes.

AL amyloidosis presenting as inflammatory polyarthritis: a case report.

Amyloidosis is a condition characterised by extracellular tissue deposition of fibrils causing a wide range of clinical manifestations. This protein deposition can occur in any tissue, most commonly in the kidney, heart, skin, peripheral nervous system, and gastrointestinal tract. However, the deposition of amyloid fibrils in the synovium is seldom reported. Musculoskeletal manifestations are subtle, subclinical and rarely the patient presents with symptoms that resemble rheumatic diseases. Here, we describe a 55-year-old man with AL (amyloid light chain) amyloidosis who presented with inflammatory polyarthritis with significant morning stiffness, inflammatory low back pain, and painful thickened tongue. The patient had anaemia, macroglossia with lateral scalloping of the tongue, papules, and plaques in the periocular, perioral and perinasal area, bilateral carpal tunnel syndrome, localised soft tissue swelling over the joints, restricted movement in different joints with flexion contractures in some joints. Rheumatoid factor and ACPA were negative and the X-ray of the sacroiliac joints was normal. We confirmed amyloidosis by biopsy of an affected skin lesion. In the urine, no Bence Jones protein was found and bone marrow study and x-ray of the skull were normal. Plasma immuno-electrophoresis and serum free light chain (FLC) assay confirmed lambda light chain type monoclonal gammopathy. Take home message: Although AL amyloidosis is a rare condition, it should be considered while evaluating atypical symptoms in patients presenting with rheumatic complaints. A high index of suspicion is necessary for proper diagnosis as delay in diagnosis will yield a poorer treatment outcome.