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Dyslipidemia, an imbalance in blood lipid levels, is a frequent complication of type 2 diabetes mellitus (DM2) and heightens the risk of cardiovascular diseases (CVDs). Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, are potent competitive inhibitors that reduce plasma cholesterol levels. However, individual responses to statins can vary markedly, possibly due to genetic variations in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene. This study aimed to investigate the pharmacogenetic relationship between the HMGCR gene and hypercholesterolemia in type 2 diabetes mellitus patients who respond differently to atorvastatin, as well as in healthy individuals. Ninety participants were involved, including sixty with type 2 diabetes mellitus and hypercholesterolemia, and thirty healthy individuals. They were randomly assigned to three groups: responsive (received atorvastatin 40 mg), non-responsive (also received atorvastatin 40 mg), and control. Both responsive and non-responsive groups underwent fasting. Biochemical tests were conducted, followed by genetic analysis to identify mutations in the HMGCR gene. The effects of statins in each group were assessed using analysis of variance (ANOVA) and post hoc Tukey's Honestly Significant Difference (HSD) analysis. Atorvastatin 40 mg was administered to assess its efficacy in reducing cholesterol levels in patients with hypercholesterolemia and type 2 diabetes mellitus. The control group exhibited similar cholesterol levels to the responsive group (cholesterol < 200 mg/dl). However, both control and responsive groups significantly differed from the non-responsive group, which had markedly elevated cholesterol levels (> 240 mg/dl). Genetic analysis revealed a cytosine nucleotide insertion in the catalytic domain of the HMGCR gene in only two non-responsive participants to atorvastatin 40 mg therapy. These two patients showed non-responsiveness to atorvastatin 40 mg due to a genetic mutation in the HMGCR gene. This mutation altered the amino acid sequence in the flap domain, replacing isoleucine with a stop codon. As a result, translation was prematurely terminated, leading to the production of truncated proteins. [ABSTRACT FROM AUTHOR]

Cancer is a significant health challenge worldwide, causing social and economic burdens. Despite advancements in medicine, it remains a leading cause of death and is projected to increase by 2040. While conventional treatments like surgery, radiation, and chemotherapy are effective, they often have severe side effects. CAR T-cell (chimeric antigen receptor T-cell) treatment is a novel immunotherapy method personalized to the patient's immune system and directly targets cancer cells. It originated in the 1980s, and advancements have made it more effective. However, challenges remain, such as severe side effects, high costs, and manufacturing variability. Despite these challenges, the treatment with CAR T-cells has shown remarkable success, especially in hematologic malignancies. Though it is new to solid tumours, ongoing research looks promising. CAR T-cell therapy offers hope for fightingcancer, and it stands poised to redefine cancer treatment paradigms, giving renewed optimism to patients globally., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)