Effect of cytokine genes in the pathogenesis and on the clinical parameters for the treatment of multiple myeloma

WOS: 000394527000002PubMed ID: 27611810In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta 1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-10 (IL-10), and clinical parameters and prognosis in patients with multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population for the first time except TNF-alpha. We analyzed five cytokine genes in 113 cases with MM and 113 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype associated with high expression in TNF-alpha gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-alpha gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-gamma (+874) variant TT genotype was increased (p = 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to controls. IFN-gamma (+874) T allele was higher inMMpatients compared with controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR = 0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with 5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival (EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR = 2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR = 0.435, p = 0.002) with negative prognostic values. Our results suggested that TNF-alpha gene (-308) AG genotype and IFN-gamma (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM

Clinical findings and mutation analysis of NF1 patients in Turkey

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that is caused by mutations of the NF1 gene. NF1 is clinically characterized by neurofibromas, pigmentation anomalies, and an increased risk of malignant tumors. The mutation rate of NF1 is one of the highest known for human disorders: approximately 50% of all affected individuals are sporadic cases and carry de novo mutations Therefore mutation analysis of NF1 may be an important tool in early diagnosis and genetic counseling. This is the first large NF1 study performed in Turkey. The data collected in this study enabled us to overview the genetic and clinical aspects of NF1 molecular diagnostics. The patients, who were clinically diagnosed for NF1, were included in this study. These patients were clinically evaluated, and subgroup of them genotyped or DNA sequenced for mutations in NF1, either to confirm the clinical diagnosis or to identify pathogenic mutations. The mutation detection rate was 52%, based on analysis of only genomic DNA. We observed that frameshift mutations were the largest proportion of the identified mutations (38.5%). The frequency of microdeletions was 26.9% and the splice site and nonsense mutations were 11.5% in this cohort. Turkish NF1 patients have similar NF1 germline mutations compared to other populations. Considering that some of these detected mutations belonged to the patients who did not fulfill the NIH criteria for NF1 diagnosis, mutation analysis of NF1 is an important tool in early diagnosis and genetic counseling.Hacettepe University Scientific Research and Development Office [H.U.BAB. 010 T02 102

MBL2 and MIF gene polymorphisms in cardiovascular patients with atherosclerotic lesions undergoing heart valve replacement

The basic underlying factor for cardiovascular diseases is atherosclerosis, which is a multifactorial disease driven by environmental and genetic factors. We aimed to study the genetic polymorphism in mannose binding lectin-2 (MBL2) and macrophage migration inhibitory factor (MIF) in the arteries of patients with atherosclerotic lesions who underwent cardiac valve replacement for cardiac valve stenosis. Thirty-five patients (38.9 %) operated with coronary bypass surgery (coronary group, CG), 55 (61.1 %) patients operated with aortic or mitral valve replacement (valve group, VG) and 100 healthy controls were analyzed for codon 54 A/B polymorphism in the MBL2 gene and –173 G/C polymorphism in the MIF gene by using the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The comparison of the healthy control group with CG and VG in terms of the MBL2 genotypes revealed significantly lower AA genotype and A allele ratios. The comparison of the healthy control group with CG and VG in terms of the MIF genotypes showed significantly lower GG genotype and G allele ratios. We suggest that the lower frequency of the GG genotype/G allele of the MIF gene and of the AA genotype/A allele of the MBL2 gene may be associated with the ethiopathogenesis of CG and VG patients