Inter and intra-ethnic differences in the distribution of the molecular variants of TPMT, UGT1A1 and MDR1 genes in the South Indian population

Umamaheswaran, Gurusamy; Kumar, Dhakchinamoorthi Krishna; Kayathiri, Dhandapani; Rajan, S; Shewade, Deepak Gopal; Dkhar, Steven Aibor; Manjunath, Sajjanavar; Ushakiran, Prayaga; Reneega, Gangadharan; Kukreti, Ritushree; Chandrasekaran, Adithan

doi:10.1007/s11033-012-1456-8

Cited by 21 publications

(15 citation statements)

References 66 publications

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“…This is the only silent polymorphism identified that might influence P-gp expression in different human tissues in different races [11]. Based on the origin and genetic nature, Indians are grouped into (i) the Indo-Aryan present in North India and (ii) the Dravidian are predominantly in south India [12]. Both origins are genetically dissimilarities for centuries.…”

Section: Ganesan Et Almentioning

confidence: 99%

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

Arumugam

2017

Asian J Pharm Clin Res

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Objective: This study was conducted to determine the frequency of C3435T and G2677T/C single nucleotide polymorphisms of multi drug resistance gene -1 (MDR1) in nephrotic syndrome (NS) children in relation to healthy subjects. The role and association of these SNPs were also determined, whether response and/or resistance to steroid treatment in children with NS in south India. Methods:Genomic DNA was isolated from 371 blood samples collected from children with NS and controls. Among 173 cases, categorized into steroid-resistant NS (SRNS) were 90 and steroid-sensitive NS (SSNS) were 83 and 198 blood samples were included as controls. All samples were subjected to DNA extraction, and polymerase chain reaction followed by restriction fragment length polymorphism for identification of C3435T and G2677T/C genomic variations. Results:The frequencies of MDR-1 C3435T, CT, TT, and CC genotypes and SNP G2677T/C GG and G allele genotypes were observed in this study group. In SRNS, children showed significantly higher frequencies of MDR-1 C3435T, CT, TT, and TT+CC genotypes were observed than SRNS and controls. The allele frequencies of SRNS children showed CC -4%, CT -32% and TT -12% and in SSNS children, CC -10.98%, CT -27.2% and TT -13.9% were observed. Furthermore, increased frequencies of MDR-1 C3435T CT, TT, TT+CC genotypes, or T allele were observed in children aged <9 years old. There were no different genotype and allele frequency observed in G2677T/C genotypes NS children and controls. Conclusion:Based on these data, we are suggesting that MDR-1 C3435T gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS as well as leads to steroid resistance. Whereas SNP G2677T/C gene polymorphisms do not have significant role observed in this study population.

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Section: Ganesan Et Almentioning

confidence: 99%

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

Arumugam

2017

Asian J Pharm Clin Res

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“…The genetic polymorphisms of TPMT [28, 29] can affect TPMT activity, which directly regulates the formation of 6-MMPNs and subsequently influences the 6-TGNs concentration. However, in some recently published articles, no correlation among TPMT activity, 6-TGNs levels and 6-MMPNs levels was observed [30].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders

Mei

Gong

et al. 2017

BMC Neurol

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BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals.MethodThirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University. The efficacy of AZA was evaluated using the expanded disability status scale (EDSS) and the annual relapse rate (ARR). The erythrocyte concentrations of AZA metabolites were detected using an LC-MS/MS method.ResultsThe erythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) were 202.03 ± 63.35 pmol/8*108 RBC and 1618.90 ± 1607.06 pmol/8*108 RBC, respectively. After the patients had received AZA therapy for more than one year, the EDSS score decreased from 5.21 ± 0.24 to 2.57 ± 0.33 (p < 0.0001), and the ARR decreased from 1.41 ± 0.23 to 0.36 ± 0.09 (p < 0.0001). The 6-TGN and 6-MMPN levels were significantly different between the non-relapsed and relapsed groups (p < 0.0001, p = 0.006, respectively). A higher ARR was significantly correlated with higher erythrocyte concentrations of 6-TGNs (p < 0.0001) and 6-MMPNs (p = 0.004).ConclusionAZA can reduce the EDSS score and ARR in NMOSD patients. Additionally, the efficacy of AZA is significantly related to the erythrocyte concentrations of 6-TGNs and 6-MMPNs. Within the safe upper limits, a higher concentration of 6-TGNs is associated with better efficacy of AZA.Trial registration number ISRCTN16551495, retrospectively registered on May 22, 2017.

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“…Though a number of studies [7][8][9][10][11][12][13][14] are available on polymorphism of TPMT gene, data on liver transplant patients are scarce from India. Hence A prospective observational study was conducted on LT patients admitted to the department of gastrointestinal surgery, Amrita Institute of Medical Sciences and Research Centre Kochi, India during 1 the objective of our study was to assess the bone marrow toxicity induced by azathioprine immunosuppressive therapy and to identify any correlation with TPMT mutation and myelosuppression in LT patients receiving azathioprine.…”

Section: Fig 1: Metabolism Pathway Of Azathioprinementioning

confidence: 99%

Pre-Screening TPMT Status of Liver Transplant Patients for Azathioprine Therapy–a Single Centre Experience From South India

Sasidharan

James

Sudhindran

2017

Int J Pharm Pharm Sci

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Objective: To assess azathioprine-induced bone marrow toxicity and its correlation with thiopurine methyltransferase (TPMT) mutation in liver transplant patients who develop myelosuppression while on azathioprine therapy. Results: A total of 76 liver transplant patients were tested for TPMT mutation. Prevalence of TPMT mutation in the study patients was 3.95%. The heterozygous TPMT*1/*3C genotype was traced in 2.63% of the patients while 1.32% of patients were homozygous for TPMT*3C allele. Interestingly 43.4% of patients with wild allele also showed azathioprine-induced myelosuppression. Azathioprine dose of 100 mg showed a higher degree of myelotoxicity than lower doses. Haematological indices of 42.1% of patients normalised on cessation of azathioprine therapy. Methods Conclusion:Myelosuppression following the introduction of azathioprine was observed in patients with both 'mutant' and 'wild-type' alleles. Therefore a cautious approach has to be taken in pre-screening liver transplant recipients for TPMT allele determination in our population. The absence of TPMT mutation does not ensure freedom from myelosuppression. Hence regular monitoring of haematological indices of such patients receiving thiopurine therapy should be continued.

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Inter and intra-ethnic differences in the distribution of the molecular variants of TPMT, UGT1A1 and MDR1 genes in the South Indian population

Cited by 21 publications

References 66 publications

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders

Pre-Screening TPMT Status of Liver Transplant Patients for Azathioprine Therapy–a Single Centre Experience From South India

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