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  1. Leung AKC, Lam JM, Leong KF, Hon KL
    Curr Pediatr Rev, 2021;17(2):76-91.
    PMID: 33302860 DOI: 10.2174/1573396316666201210125858
    BACKGROUND: Vitiligo is a relatively common acquired pigmentation disorder that can cause significant psychological stress and stigmatism.

    OBJECTIVE: This article aims to familiarize physicians with the clinical manifestations, evaluation, diagnosis, and management of vitiligo.

    METHODS: A Pubmed search was conducted in Clinical Queries using the key term "vitiligo". The search included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English language. The information retrieved from the above search was used in the compilation of the present article.

    RESULTS: Approximately one quarter of patients with vitiligo have the onset before 10 years of age. Genetic, immunological, neurogenic and environmental factors may have a role to play in the pathogenesis. Vitiligo typically presents as acquired depigmented, well-demarcated macules/patches that appear milk- or chalk-white in color. Lesions tend to increase in number and enlarge centrifugally in size with time. Sites of predilection include the face, followed by the neck, lower limbs, trunk, and upper limbs. The clinical course is generally unpredictable. In children with fair skin, no active treatment is usually necessary other than the use of sunscreens and camouflage cosmetics. If treatment is preferred for cosmesis, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the mainstays of treatment.

    CONCLUSION: The therapeutic effect of all the treatment modalities varies considerably from individual to individual. As such, treatment must be individualized. In general, the best treatment response is seen in younger patients, recent disease onset, darker skin types, and head and neck lesions. Topical corticosteroids and calcineurin inhibitors are the treatment choice for those with localized disease. Topical calcineurin inhibitors are generally preferred for lesions on genitalia, intertriginous areas, face, and neck. Narrowband ultraviolet B phototherapy should be considered in patients who have widespread vitiligo or those with localized vitiligo associated with a significant impact on the quality of life who do not respond to treatment with topical corticosteroids and calcineurin inhibitors.

    Matched MeSH terms: Calcineurin Inhibitors/therapeutic use
  2. Goh CKW, Silvester J, Wan Mahadi WNS, Chin LP, Ying LT, Leow TC, et al.
    Protein Eng. Des. Sel., 2018 12 01;31(12):489-498.
    PMID: 31120120 DOI: 10.1093/protein/gzz008
    The FK506-binding protein of Plasmodium knowlesi (Pk-FKBP35) is considerably a viable antimalarial drug target, which belongs to the peptidyl-prolyl cis-trans isomerase (PPIase) protein family member. Structurally, this protein consists of an N-terminal FK506-binding domain (FKBD) and a C-terminal tetratricopeptide repeat domain (TPRD). This study aims to decipher functional properties of these domains as a platform for development of novel antimalarial drugs. Accordingly, full-length Pk-FKBP35 as well as its isolated domains, Pk-FKBD and Pk-TPRD were overexpressed, purified, and characterized. The results showed that catalytic PPIase activity was confined to the full-length Pk-FKBP35 and Pk-FKBD, suggesting that the catalytic activity is structurally regulated by the FKBD. Meanwhile, oligomerization analysis revealed that Pk-TPRD is essential for dimerization. Asp55, Arg60, Trp77 and Phe117 in the Pk-FKBD were considerably important for catalysis as underlined by significant reduction of PPIase activity upon mutations at these residues. Further, inhibition activity of Pk-FKBP35 towards calcineurin phosphatase activity revealed that the presence of FKBD is essential for the inhibitory property, while TPRD may be important for efficient binding to calcineurin. We then discussed possible roles of FKBP35 in Plasmodium cells and proposed mechanisms by which the immunosuppressive drug, FK506, interacts with the protein.
    Matched MeSH terms: Calcineurin/metabolism
  3. Leung AK, Lam JM, Leong KF, Hon KL
    Drugs Context, 2020;9.
    PMID: 32742295 DOI: 10.7573/dic.2020-5-6
    Background: Tinea corporis is a common fungal infection that mimics many other annular lesions. Physicians must familiarize themselves with this condition and its treatment.

    Objective: This article aimed to provide a narrative updated review on the evaluation, diagnosis, and treatment of tinea corporis.

    Methods: A PubMed search was performed with Clinical Queries using the key term 'tinea corporis.' The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies, and reviews. The search was restricted to the English language. The information retrieved from the mentioned search was used in the compilation of the present article.

    Results: Tinea corporis typically presents as a well-demarcated, sharply circumscribed, oval or circular, mildly erythematous, scaly patch or plaque with a raised leading edge. Mild pruritus is common. The diagnosis is often clinical but can be difficult with prior use of medications, such as calcineurin inhibitors or corticosteroids. Dermoscopy is a useful and non-invasive diagnostic tool. If necessary, the diagnosis can be confirmed by microscopic examination of potassium hydroxide wet-mount preparations of skin scrapings from the active border of the lesion. Fungal culture is the gold standard to diagnose dermatophytosis especially if the diagnosis is in doubt and results of other tests are inconclusive or the infection is widespread, severe, or resistant to treatment. The standard treatment of tinea corporis is with topical antifungals. Systemic antifungal treatment is indicated if the lesion is multiple, extensive, deep, recurrent, chronic, or unresponsive to topical antifungal treatment, or if the patient is immunodeficient.

    Conclusion: The diagnosis of tinea corporis is usually clinical and should pose no problem to the physician provided the lesion is typical. However, many clinical variants of tinea corporis exist, rendering the diagnosis difficult especially with prior use of medications, such as calcineurin inhibitors or corticosteroids. As such, physicians must be familiar with this condition so that an accurate diagnosis can be made and appropriate treatment initiated.

    Matched MeSH terms: Calcineurin Inhibitors
  4. Acharya M, Singh N, Gupta G, Tambuwala MM, Aljabali AAA, Chellappan DK, et al.
    Cell Signal, 2024 Apr;116:111043.
    PMID: 38211841 DOI: 10.1016/j.cellsig.2024.111043
    Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
    Matched MeSH terms: Calcineurin
  5. Choong CL, Wong HS, Lee FY, Lee CK, Kho JV, Lai YX, et al.
    Transplant Proc, 2018 Oct;50(8):2515-2520.
    PMID: 30316389 DOI: 10.1016/j.transproceed.2018.04.024
    BACKGROUND: Inhibition of calcineurin inhibitor (CNI) metabolism with diltiazem reduces the dose of tacrolimus required to achieve its therapeutic blood concentration in kidney transplant recipients (KTRs). This cost-savings maneuver is practiced in several countries, including Malaysia, but the actual impacts of diltiazem on tacrolimus blood concentration, dose-response relationship, cost-savings, and safety aspects are unknown.

    METHODS: This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC0) and other relevant clinical data for 70 eligible KTRs were reviewed.

    RESULTS: The dose of 1 mg tacrolimus resulted in a median TacC0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus (P < .01). A further 90-mg increase in diltiazem to 180 mg/d resulted in a further increase of TacC0 to 1.66 ± 2.58 ng/mL/mg tacrolimus (P = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [P < .01]). Addition of 180 mg/d diltiazem reduced the required tacrolimus dose to 4 mg/d, resulting in a cost-savings of USD 2045.92 per year (per patient) at our center. Adverse effects reported within 3 months of diltiazem introduction were bradycardia (1.4%) and postural hypotension (1.4%), which resolved after diltiazem dose reduction.

    CONCLUSION: Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.

    Matched MeSH terms: Calcineurin Inhibitors/administration & dosage
  6. de Luca Montes RA, Huq M, Godfrey T, Oon S, Calderone A, Kandane-Rathnayake R, et al.
    Adv Rheumatol, 2024 May 08;64(1):38.
    PMID: 38720354 DOI: 10.1186/s42358-024-00366-y
    BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.

    METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.

    RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.

    CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

    Matched MeSH terms: Calcineurin Inhibitors/therapeutic use
  7. Wong WF, Looi CY, Kon S, Movahed E, Funaki T, Chang LY, et al.
    Eur J Immunol, 2014 Mar;44(3):894-904.
    PMID: 24310293 DOI: 10.1002/eji.201343496
    Runx1 transcription factor is a key player in the development and function of T cells. Runx1 transcripts consist of two closely related isoforms (proximal and distal Runx1) whose expressions are regulated by different promoters. Which Runx1 isoform is expressed appears to be tightly regulated. The regulatory mechanism for differential transcription is, however, not fully understood. In this study, we investigated the regulation of the proximal Runx1 promoter in T cells. We showed that proximal Runx1 was expressed at a low level in naïve T cells from C57BL/6 mice, but its expression was remarkably induced upon T-cell activation. In the promoter of proximal Runx1, a highly conserved region was identified which spans from -412 to the transcription start site and harbors a NFAT binding site. In a luciferase reporter assay, this region was found to be responsive to T-cell activation through Lck and calcineurin pathways. Mutagenesis studies and chromatin immunoprecipitation assay indicated that the NFAT site was essential for NFAT binding and transactivation of the proximal Runx1 promoter. Furthermore, TCR signaling-induced expression of proximal Runx1 was blocked by treatment of cells with cyclosporin A. Together, these results demonstrate that the calcineurin-NFAT pathway regulates proximal Runx1 transcription upon TCR stimulation.
    Matched MeSH terms: Calcineurin/metabolism*
  8. Lim WF, Mohamad Yusof MI, Teh LK, Salleh MZ
    Nutrients, 2020 Sep 30;12(10).
    PMID: 33007803 DOI: 10.3390/nu12102993
    Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive values of the combined mixture of moringa leaves and seed residue (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on the primary mammary epithelial cells (PMECs), non-malignant Chang's liver cells and various human cancer cell lines (including breast, cervical, colon and liver cancer cell lines). The MOLSr ratio with the most potent cytotoxic activity was used in xenograft mice injected with MDA-MB-231 cells for in vivo tumorigenicity study as well as further protein and gene expression studies. M1S9, specifically composed of saponin and amino acid, retained the lowest antioxidant activity but the highest glucosinolate content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMECs after treatment with M1S9. Solid tumor from MDA-MB-231 xenograft mice was inhibited by up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention potential of MOLSr extracts in a breast cancer model; however, the precise mechanism warrants further investigation.
    Matched MeSH terms: Calcineurin
  9. Luk D, Hon KLE, Dizon MVC, Leong KF, Tay YK, Koh MJ, et al.
    Dermatol Ther (Heidelb), 2021 Feb;11(1):275-291.
    PMID: 33313998 DOI: 10.1007/s13555-020-00467-8
    INTRODUCTION: There is some evidence to suggest that the prevalence of atopic dermatitis (AD) in Asia is rising. We have therefore developed an algorithm for the topical treatment of AD throughout South and East Asia for use by primary care physicians, pediatricians and dermatologists.

    METHODS: Nine AD experts from South and East Asia and one from Europe developed the algorithm based upon treatment guidelines, relevant literature and local treatment practices. The algorithm outlines current best practice for the use of emollients, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with the intention of simplifying the treatment regimen of mild-to-moderate AD in South and East Asia.

    RESULTS: Patients with AD should bathe and cleanse affected skin to remove crusts and scales daily. Emollients should also be applied daily as a maintenance treatment. When selecting appropriate topical anti-inflammatory treatment for AD flares, several factors should be taken into consideration, including the patient's age, attitude to treatment options and site of AD lesions. Given the concerns regarding the risk of skin atrophy with use of TCS, a TCI should be used to treat AD lesions in sensitive skin areas: pimecrolimus is recommended for mild-to-moderate AD in these locations, while tacrolimus should be considered for moderate and severe cases. Either pimecrolimus or tacrolimus is recommended for flares in other, non-sensitive body locations. A proactive or intermittent maintenance treatment strategy involving regular emollient use and twice-weekly application of a TCI to previously affected areas is encouraged to reduce the risk of flares.

    CONCLUSIONS: The algorithm proposed here is intended to simplify the topical treatment of mild-to-moderate AD in daily practice in South and East Asian countries.

    Matched MeSH terms: Calcineurin Inhibitors
  10. Zulkifli MH, Viswenaden P, Jasamai M, Azmi N, Yaakob NS
    Biomed Pharmacother, 2019 Feb 20;112:108630.
    PMID: 30797147 DOI: 10.1016/j.biopha.2019.108630
    5-HT3R antagonists such as ondansetron, granisetron and tropisetron have been clinically used to treat nausea and vomiting in chemotherapy patients. However, current study and research revealed novel potentials of these ligands in other diseases like inflammation, Alzheimer's, and drug abuse. Towards utilising these drugs as anti-smoking agents to treat nicotine dependence problem, there are conflicting reports regarding the potential of these ligands in modulating the effects of nicotine in both human and animal behavioural studies. This is complicated by the heterogeneity of 5-HT3R itself, cross regulation between nicotinic acetylcholinergic receptor (nAChR) and distinct pharmacological profiles of 5-HT3R antagonists. This review gathered existing studies conducted investigating the potential of "-setron" class of 5-HT3R antagonists in modulating nicotine effects. We proposed that the mechanism where 5-HT3R antagonists mediate the effects of nicotine could be attributed by both direct at 5-HT3R and indirect mechanism in nicotine addiction downstream regulation. The indirect mechanism mediated by the 5-HT3R antagonist could be through α7 nAChR, 5-HT1B receptor (5-HT1BR), 5-HT1C receptor (5-HT1CR), calcineurin activity, p38 MAPK level, PPAR-γ and NF-κβ. Our review suggested that future studies should focus on newer 5-HT3R antagonist with superior pharmacological profile or the one with multitarget action rather than high selectivity at single receptor.
    Matched MeSH terms: Calcineurin
  11. Chow S, Seow CS, Dizon MV, Godse K, Foong H, Chan V, et al.
    Asia Pac Allergy, 2018 Oct;8(4):e41.
    PMID: 30402408 DOI: 10.5415/apallergy.2018.8.e41
    Background: Atopic dermatitis (AD) is a common skin condition among Asians. Recent studies have shown that Asian AD has a unique clinical and immunologic phenotype compared with European/American AD.

    Objective: The Asian Academy of Dermatology and Venereology Expert Panel on Atopic Dermatitis developed this reference guide to provide a holistic and evidence-based approach in managing AD among Asians.

    Methods: Electronic searches were performed to retrieve relevant systematic reviews and guidelines on AD. Recommendations were appraised for level of evidence and strength of recommendation based on the U.K. National Institute for Health and Care Excellence and Scottish Intercollegiate Guidelines Network guidelines. These practice points were based on the consensus recommendations discussed during the Asia Pacific Meeting of Experts in Dermatology held in Bali, Indonesia in October 2016 and April 2017.

    Results: The Expert Panel recommends an approach to treatment based on disease severity. The use of moisturizers is recommended across all levels of AD severity, while topical steroids are recommended only for flares not controlled by conventional skin care and moisturizers. Causes of waning efficacy must be explored before using topical corticosteroids of higher potency. Topical calcineurin inhibitors are recommended for patients who have become recalcitrant to steroid, in chronic uninterrupted use, and when there is steroid atrophy, or when there is a need to treat sensitive areas and pediatric patients. Systemic steroids have a limited role in AD treatment and should be avoided if possible. Educational programs that allow a patient-centered approach in AD management are recommended as an adjunct to conventional therapies. Recommendations on the use of phototherapy, systemic drugs, and emerging treatments are also included.

    Conclusion: The management of AD among Asians requires a holistic approach, integrating evidence-based treatments while considering accessibility and cultural acceptability.

    Matched MeSH terms: Calcineurin Inhibitors
  12. Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN
    Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
    PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077
    Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.
    Matched MeSH terms: Calcineurin Inhibitors*
  13. Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.
    BMC Nephrol, 2020 09 07;21(1):388.
    PMID: 32894076 DOI: 10.1186/s12882-020-02052-9
    BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

    METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

    RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

    CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

    Matched MeSH terms: Calcineurin Inhibitors
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