Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers.

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2-51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63-87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers.

Importance: Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. Objective: To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. Design, Setting, and Participants: This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. Intervention: Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. Main Outcomes and Measures: Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. Results: This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. Conclusions and Relevance: This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. Trial Registration: ClinicalTrials.gov Identifier: NCT04377360.

Evaluation of pharmacological efficacy and safety of hydroxyurea in sickle cell disease: Study of a pediatric cohort from Chhattisgarh, India.

Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical -severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sß patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring.

A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia.

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

Rapid and accurate nucleobase detection using FnCas9 and its application in COVID-19 diagnosis.

Rapid detection of DNA/RNA pathogenic sequences or variants through point-of-care diagnostics is valuable for accelerated clinical prognosis, as witnessed during the recent COVID-19 outbreak. Traditional methods relying on qPCR or sequencing are tough to implement with limited resources, necessitating the development of accurate and robust alternative strategies. Here, we report FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that utilizes a direct Cas9 based enzymatic readout for detecting nucleobase and nucleotide sequences without trans-cleavage of reporter molecules. We also demonstrate that FELUDA is 100% accurate in detecting single nucleotide variants (SNVs), including heterozygous carriers, and present a simple web-tool JATAYU to aid end-users. FELUDA is semi-quantitative, can adapt to multiple signal detection platforms, and deploy for versatile applications such as molecular diagnosis during infectious disease outbreaks like COVID-19. Employing a lateral flow readout, FELUDA shows 100% sensitivity and 97% specificity across all ranges of viral loads in clinical samples within 1hr. In combination with RT-RPA and a smartphone application True Outcome Predicted via Strip Evaluation (TOPSE), we present a prototype for FELUDA for CoV-2 detection closer to home.

Methylenetetrahydrofolate reductase polymorphisms as genetic markers to predict homocysteinemia and clinical severity in sickle cell disease.

Aim: The present study observed the relationship between the methylenetetrahydrofolate reductase genotypes and clinical outcome in children with sickle cell disorder. Methodology: A total of 249 children were recruited for the study and evaluated clinically for calculating severity score, homocysteine levels and C677T and A1298C genotyping. Results: The frequencies of variant genotypes were 28.1% CT/TT677 and 69.1% AC/CC1298. Plasma homocysteine was significantly elevated in variant groups (p < 0.001). Both the genotypes accorded significant association with homocysteinemia (p < 0.001). Vascular crisis (p = 0.04), frequency of hospitalization (p < 0.001) and severity score (p = 0.02) revealed association with C677T and not with A1298C. The CT/TT677 genotypes showed 3.39-times (p = 0.032) increase in a higher score for severity. Conclusion: C677T depicted significant association with clinical severity in study population.

Identification of therapeutic targets for inflammation in sickle cell disease (SCD) among Indian patients using gene expression data analysis.

Sickle cell disease (SCD) is life-threatening hemoglobinopathy prevalent in India, Sub-Saharan Africa and Middle East. Inflammation plays a pivotal role in disease process and involves intricate interaction among leukocytes, platelets, sickle erythrocytes and vascular endothelium. Available disease modifying therapies are hydroxyl-urea and blood transfusion. Therefore, it is of interest to develop improved pharmacological agents for SCD. We report up-regulated genes in steady state and vaso-occlusive crisis using analysis of gene expression data obtained by microarray experiment for SCD as potential targets. The association of these targets with inflammation in pathway analysis is also documented.

Enhanced chondrogenesis of mesenchymal stem cells over silk fibroin/chitosan-chondroitin sulfate three dimensional scaffold in dynamic culture condition.

Chondroitin sulfate (Ch) is one of the main structural components of cartilage tissue, therefore, its presence in tissue engineered scaffold is expected to enhance cartilage regeneration. Previously, silk fibroin/chitosan (SF/CS) blend was proven to be a potential biomaterial for tissue development. In this study, the effect of Ch on physicochemical and biological properties of SF/CS blend was investigated and scaffolds with 0.8 wt% Ch was found to be favorable. The scaffolds possess pore size of 37-212 µm, contact angle 46.2-50.3°, showed controlled swelling and biodegradation. The biocompatibility of scaffold was confirmed by subcutaneous implantation in mouse. Human mesenchymal stem cells (hMSCs) seeded scaffolds cultured under spinner flask bioreactor promoted cell attachment, proliferation, distribution, and metabolic activity in vitro. The histology and immunofluorescence studies revealed that combined effect of Ch and dynamic condition resulted in higher glycosaminoglycan secretion and native cartilage type matrix synthesis in comparison to SF/CS scaffolds used as control. Higher expression of collagen-II, Sox9, aggrecan and decrease in collagen-I expression represented by quantitative polymerase chain reaction study confirmed the progression of chondrogenic differentiation. This study successfully demonstrates the potentiality of SF/CS-Ch scaffold for hMSCs recruitment and redirecting cartilage tissue regeneration with enhanced chondrogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2576-2587, 2018.

Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs.

It is documented that human mesenchymal stem cells (hMSCs) can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK) inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

Understanding the molecular mechanism of improved proliferation and osteogenic potential of human mesenchymal stem cells grown on a polyelectrolyte complex derived from non-mulberry silk fibroin and chitosan.

The development of engineered bone tissue, as a promising alternative to conventional bone grafts, has so far not proven successful and still remains challenging. Thus, attempts have been made in the present study to synthesize polyelectrolyte complex (PEC) scaffolds by blending chitosan (CS) to silk fibroin (SF) derived from the non-mulberry silkworm (Antheraea pernyi) at three different pH values (5.0, 6.0, and 7.0), and to characterize them in terms of morphology, ultrastructure and mechanical properties with scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy, x-ray diffraction and tensile strength analyses. The prepared PEC scaffolds showed a mean pore size of 130 µm, as revealed by SEM analysis, and a comparatively higher compressive strength. The findings of in vitro cytocompatibility, in vivo biocompatibility and osteogenic marker (genes/proteins) analysis suggest that the PECs blended at pH 7.0 showed greater stability and enhanced growth and an osteogenic differentiation capability of human mesenchymal stem cells (MSCs). To aid our understanding of protein-polyion binding mechanisms, we employed a molecular docking and simulation study of SF macrodomains and CS oligomer using Schrödinger 14 and GROMACS (Groningen Machine for Chemical Simulations) software. The study involved analytical techniques for macromolecular solution characterization and theoretical simulations based on molecular dynamics. The computational studies confirmed the presence of an integral RGD sequence that played a vital role in superior cell-attachment, proliferation and osteogenic differentiation of MSCs grown on the developed SF-CS PEC scaffolds.

Structure elucidation and in silico docking studies of a novel furopyrimidine antibiotics synthesized by endolithic bacterium Actinomadura sp. AL2.

On screening of endolithic actinobacteria from a granite rock sample of Meghalaya for antibacterial compound, a novel antibacterial compound CCp1 was isolated from the fermentation broth of Actinomadura sp. AL2. On purification of the compound based on chromatographic techniques followed by characterization with FT-IR, UV-visible, 1H NMR, 13C NMR and mass spectrometry, the molecular formula of the compound was generated as C20H17N3O2, a furopyrimidine derivative. In vitro antibacterial activity of the compound was evaluated against both Gram positive and negative bacteria by agar well diffusion assay. The compound had lowest MIC (2.00 µg/ml) for Bacillus subtilis and highest MIC (> 64 µg/ml) for Staphylococcus epidermidis and Pseudomonas aeruginosa. The study revealed that the compound has potential antibacterial activity. The mode of action of the antibacterial compound was evaluated through in silico studies for its ability to bind DNA gyrase, 30S RNA molecules, OmpF porins and N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU). The antibacterial compound demonstrated more favorable docking with DNA gyrase, 30S RNA molecules and OmpF porins than GlmU which support the antibacterial compound CCp1 can be as a promising broad spectrum antibiotic agent with "multitarget" characteristics.

Selaginella bryopteris Aqueous Extract Improves Stability and Function of Cryopreserved Human Mesenchymal Stem Cells.

The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs.

Mesenchymal stem cell in venous leg ulcer: An intoxicating therapy.

Venous leg ulcers (VLU) are a prevalent and reoccurring type of complicated wound, turning as a considerable public healthcare issue, with critical social and economic concern. There are both medical and surgical therapies to treat venous leg ulcers; however, a cure does not yet exist. Mesenchymal stem cells (MSC) are capable and proved of accelerating wound healing in vivo and their study with human chronic wounds is currently awaited. MSCs are a promising source of adult progenitor cells for cellular therapy and have been demonstrated to differentiate into various mesenchymal cell lineages. They have a crucial and integral role in native wound healing by regulating immune response and inflammation. Improved understanding of the cellular and molecular mechanisms at work in delayed wound healing compels to the development of cellular therapy in VLU. This review focuses on the current treatment option of VLU and further emphasizing the role of MSCs in accelerating the healing process. With further understanding of the mechanism of action of these cells in wound improvement and, the involvement of cytokines can also be revealed that could be used for the therapeutic purpose for VLU healing. Clinical uses of MSCs have been started already, and induced MSCs are surely a promising tool or compelling therapy for VLU.

Autophagy Activation Alleviates Amyloid-ß-Induced Oxidative Stress, Apoptosis and Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells.

Autophagy is an evolutionary conserved catabolic process that ensures continuous removal of damaged cell organelles and long-lived protein aggregates to maintain cellular homeostasis. Although autophagy has been implicated in amyloid-ß (Aß) production and deposition, its role in pathogenesis of Alzheimer's disease remains elusive. Thus, the present study was undertaken to assess the cytoprotective and neuroprotective potential of autophagy on Aß-induced oxidative stress, apoptosis and neurotoxicity in human neuroblastoma SH-SY5Y cells. The treatment of Aß1-42 impaired the cell growth and redox balance, and induced apoptosis and neurotoxicity in SH-SY5Y cells. Next, the treatment of rapamycin (RAP) significantly elevated the expression of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), sequestosome-1/p62, Beclin-1, and unc-51-like kinase-1 (ULK1) in SH-SY5Y cells. RAP-induced activation of autophagy notably alleviated the Aß1-42-induced impairment of redox balance by decreasing the levels of pro-oxidants such as reactive oxygen species, lipid peroxidation and Ca2+ influx, and concurrently increasing the levels of antioxidant enzymes such as superoxide dismutase and catalase. The RAP-induced autophagy also ameliorated Aß1-42-induced loss of mitochondrial membrane potential and apoptosis. Additionally, the activated autophagy provided significant neuroprotection against Aß1-42-induced neurotoxicity by elevating the expression of neuronal markers such as synapsin-I, PSD95, NCAM, and CREB. However, 3-methyladenine treatment significantly exacerbated the neurotoxic effects of Aß1-42. Taken together, our study demonstrated that the activation of autophagy provided possible neuroprotection against Aß-induced cytotoxicity, oxidative stress, apoptosis, and neurotoxicity in SH-SY5Y neuronal cells.

Assessment of renal function in Indian patients with sickle cell disease.

Sickle cell disease (SCD) and its variants are genetic disorders resulting from the presence of a mutated form of hemoglobin. Renal disease is one of the most frequent complications, and kidney damage starts very early and progresses throughout life causing severe complications. The present study is aimed to analyze creatinine-based estimated glomerular filtration rate (eGFR) in 616 SCD patients (507 HbSS and 109 HbSB+), receiving medical care at outpatient wing of Sickle Cell Institute, Chhattisgarh. Glomerular filtration rate (GFR) estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault, chronic kidney disease epidemiology collaboration (CKD-EPI) (<17 years analyzed with Schwartz), and SCD specific Jamaica Sickle Cell Cohort Study (JSCCS)-GFR equations were compared. Further, eGFR calculated using the CKD-EPI and Schwartz equations was used to define various stages of kidney function and compared with clinical and hematological variables. The mean age of patients was 15.8 years. Comparison of eGFR using various formulas revealed that MDRD and JSCCS formulas overestimated the GFR. Among SCD patients, prevalence of glomerular hyperfiltration (GHF) is high followed by renal insufficiency (RI) and renal failure (RF). However, no differences were found in hematological profiling among different functional stages of kidney. Age and body surface area are significantly more in SCD individuals with normal kidney function and GHF. Participants with RF showed a higher level of blood urea and fetal hemoglobin. In summary, this is the first study to analyze different functional stages of kidney among SCD patients of India. Our study revealed that the GHF and RI are the important indicators of kidney damage.

Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the incidence of cervical cancer in Chhattisgarh.

Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All subjects were genotyped for CYP1A1m1 (T>C) and m2 (A>G) using PCR-RFLP with statistical analysis by using SPSS version 16.0 and VassarStats (online). Among the two gene variants rs4646903 (T>C) and rs1048943 (A>G), individuals with AG and GG genotypes of CYP1A1m2 polymorphism have significantly higher and increased risk of cervical cancer (OR=2.0, 95%CI=1.04-3.84, p=0.035; OR=62.9, 95%CI=3.72-1063.83, p=0.004 respectively) and the association of CYP1A1m1 polymorphism did not show any significant relationship with cervical cancer patients (p=0.23). The 'G' allele showed strong association with the disease (p<0.0001). Thus, CYP1A1m2 polymorphism showed an increased risk in the population leading to cervical cancer. Our study suggested that the presence of 'C' allele of rs4646903 (T>C) showed no risk and 'G' allele of rs1048943 (A>G) might be a leading allele to cause increased cervical cancer susceptibility due to significant association of CYP1A1m2 gene polymorphism.

Assessment of Serum Vascular Endothelial Growth Factor Levels in Pregnancy-Induced Hypertension Patients.

Objective. The objective of the study was to assess the serum vascular endothelial growth factor (VEGF) levels in peripheral blood of patients with pregnancy-induced hypertension (PIH) and find association between serum VEGF levels and PIH. Methods. Thirty-five PIH subjects, 35 normal pregnant females, and 20 normal healthy females were included in the study. Detailed history, clinical examination, and relevant biochemical parameters were assessed; serum VEGF levels were estimated using Double-antibody enzyme-linked immunosorbent assay. Results. The study groups were found to be age matched (p = 0.38). VEGF level in the pregnancy-induced hypertensive group (median = 109.19 (3.38 ± 619)) was significantly higher than the normal pregnant (median = 20.82 (1.7-619)) and control (median = 4.92 (1.13-13.07)) group and the difference between these three groups was significant (p < 0.0001). The 3 groups are found to be significantly different in terms of RBS (p = 0.01), urea (p < 0.0001), creatinine (p = 0.0005), AST (p = 0.0032), ALT (p = 0.0007), total protein (p = 0.0004), albumin (p < 0.0001), calcium (p = 0.001), and sodium (p = 0.02), while no statistically significant difference was found between total bilirubin (p = 0.167), direct bilirubin (p = 0.07), uric acid (p = 0.16), and potassium (p = 0.14). Conclusion. Significantly higher levels of serum VEGF were noted in PIH subjects compared to normal pregnant and control subjects.

Hb F Levels in Indian Sickle Cell Patients and Association with the HBB Locus Variant rs10128556 (C>T), and the HBG XmnI (Arab-Indian) Variant.

The prevalence of sickle cell disease in India is very high. Hb F is one of the most powerful modulators of disease severity in sickle cell disease patients. It was traditionally thought that the disease is milder in Indian sickle cell disease patients predominantly due to the Arab-Indian haplotype characterized by the HBG XmnI [rs7482144 (G>A)] variant, which is associated with increased Hb F levels. In the current study, we investigated the Hb F levels in individuals with the rs10128556 (C>T) variant and also determined its linkage with the HBG XmnI variant. The present study was conducted on a cohort of 275 individuals, which consisted of 221 patients with sickle cell disease and 54 patients with sickle cell trait. Analysis of hemoglobin (Hb) fractions and variants was done on the high performance liquid chromatography (HPLC) system. Genotyping for rs10128556 was done by direct sequencing of the products. Mean Hb F levels in the sickle cell disease patients was 19.36 ± 6.79. The genotypic frequencies for rs10128556 were 82.0% (TT), 16.7% (CT) and 1.3% (CC) for sickle cell disease patients. The minor C allele resulted in 52.0% decrease in Hb F levels when homozygous and 7.0% decrease when heterozygous. The rs10128556 single nucleotide polymorphism (SNP) was in strong but not complete linkage with the HBG XmnI variant. In conclusion, the study determined for the first time the frequency and association of rs10128556 in Indian sickle cell disease patients with Hb F. It also established that it was not in complete linkage with the HBG XmnI variant in this high risk population.