Effects of TNFα, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters, Prognosis and Survival of Multiple Myeloma Cases.

C Basmaci,S Oguzkan-Balci,M Yilmaz,M Pehlivan,T Sever,S Pehlivan,V Okan,Ag Tomatir

doi:10.7314/apjcp.2016.17.3.1009

C Basmaci, S Oguzkan-Balci + Show 6 more

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https://doi.org/10.7314/apjcp.2016.17.3.1009

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Abstract

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFα), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFα, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNF α(-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFαgene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNF α(-308) GG genotypes may have roles in myeloma pathogenesis.

Highlights

Genetic variation is common across the human genome
We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD, MP, autolougus stem cell transplantation (ASCT), BODEC and TD
There was no significant difference between NOS3, TNFα and MDR1 gene polymorphism compared with the factors which have impact on overall survival such as gender, age, stage, Eastern Cooperative Oncology Group (ECOG), lactate dehidrogenase (LDH), c-reactive protein (CRP), first line treatment and response to first line treatment

Summary

Introduction

Genetic variation is common across the human genome. It is estimated that there are more than 7 million single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% to 10%. ENOS on chromosome 7q 35-36 takes an important role in homeostasis (Bivalacqua et al, 2002) Variations on this gene may result in decrease of NO synthesis and cause several diseases (Heil et al, 2006; Game et al, 2013). Genetic factors including single nucleotide polymorphisms (SNPs) that change cytochrome P450 (CYP) activity and epigenetic regülation that modifies CYP expression levels may contribute to the change in pharmocokinetics and adverse drug reactions (ADRs) (Nakamura et al, 2013). We investigated relationship between TNFα, NOS3, MDR1 genes polymorphisms and clinical parameters, prognosis and survival for the VAD (Vincristine-AdriamycineDexamethasone), MP (Mephalane-Prednisolone), autologous stem cell transplantation (ASCT), BODEC (Bortezomib-Dexamethasone-Cyclophosphamide) and TD (Thalidomide-Dexamethasone) treatment of multiple myeloma

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