>Magister Scientiae - MSc / The burden of non-communicable diseases (NCDs) in South Africa is predicted to increase substantially in the next decades if the necessary preventative measures are not taken. The two most common NCDs associated with rapid mortality increase are diabetes mellitus (DM) and hypertension (HTN). Both of these diseases, i.e DM and HTN, can be a result of a combination of modifiable risk factors (behavioral) and non-modifiable risk factors (genetic, physiological, and environmental). New strategies implemented to manage these diseases should include addressing both modifiable and non-modifiable risk factors for patients with NCDs. The aim of this study was to contribute to the reduction of incidence of uncontrolled T2DM among patients taking metformin as a first-line anti-diabetic drug, through the development of individualized therapy for this drug. When implemented, this could be one of the healthcare strategies to address non-modifiable risk factors for patients with T2DM as an important NCD. The first objective of the study was to explore the prevalence and risk factors of DM and HTN in South Africa, especially within the economically disadvantaged population.

>Magister Scientiae - MSc / As human beings we are curious about our origin and ancestry. A curiosity has led to an investigation of human evolution and expansion across the world by means of population genetics and phylo-genetics by evaluating a region in Southern Africa that is largely unknown. The objective of this study was to develop a quick, inexpensive and accurate hierarchical diagnostic screening system of the MtDNA phylogenetic tree, AI-SNPs in the mtDNA genome by using High Resolution Melting analysis to evaluate the population composition and ancestral haplogroups of Southern African populations in Limpopo. The admixture between the ‘Khoesan’ hunter-gatherers, herders and the Bantu speaking populations led to population growth and expansion in Limpopo. This has contributed to populations settling in Limpopo and has thus shaped the ancestral contemporary populations. No research on these individuals residing in Limpopo has been done before, thus an investigation of their ancestral origin was necessary. A total of 760 saliva samples were collected from individuals residing in Limpopo. Only 500 saliva samples were extracted by means of an optimized salting out technique. Five hundred extracted genomic samples were genotyped by means of a quick, inexpensive High-resolution melting analysis. Of the 500 samples, the genotyping results showed 95 individuals derived for the L3 haplogroup which gives a 19% ratio of individuals screened with Multiplex 1. Only 56 individuals were derived for the L1 haplogroup, which gives a percentage of 11%. A total of 249 individuals were derived for the L0 haplogroup, making up a 50% of the total individuals genotyped. Only 100 samples were derived for L0a, making up 20% of individuals screened with Multiplex 1. Of the 95 samples derived for the L3 haplogroup, the results showed 87 individuals to be ancestral for both M and N, making up 91.57% of individuals screened with Multiplex 2. http://etd.uwc.ac.za/. In population genetics using SNPs to infer population history and ancestral origin has become significant, this study allowed researchers to evaluate population groups by investigating their genetic markers and the application of the results allowed for downstream analyses. Finally, this study provides a quick and simple screening method for the selection of lineages that are of interest for further studies.

Thesis (M. Sc. Agriculture (Animal Production)) -- University of Limpopo, 2022 / Weighing scales are typically out of reach for small-scale farmers due to expensive cost and a lack of operational expertise. However, understanding body weight and its relationship to linear body measures are critical for farmers making management decisions. Single nucleotide polymorphisms (SNPs) are significant because they influence the coding area of the DNA, leading to changes to the amino acid sequences, which might affect the animal's phenotype. The current study sought to find genetic indicators of the insulin-like growth factor 1 gene that may be exploited for breeding selection in order to improve the growth traits of Kalahari Red goats. The research was carried out at the Zuurfontein farm in Polokwane. As experimental animals, fifty (n = 50) Kalahari Red goats (8 males and 42 females) aged 2 to 3 years were used. A balance weighing scale was used to record body weight, and a measuring tape was used to capture linear body measures. Blood samples were obtained from the jugular vein once per animal using vacutainer blood collecting tubes. The deoxyribonucleic acid (DNA) was extracted and purified according to the methodology provided by Noegen's Genomic DNA isolation kit. Pearson’s correlation was used to achieve the correlation between the growth traits, Simple linear regression was performed to predict body weight from linear body measurements, Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was utilized to discover the single nucleotide polymorphism, Chi-square test (χ2) was performed to assess the allele frequencies for Hardy-Weinberg equilibrium and General Linear Model (GLM) was performed for marker-trait association analysis. The mean square error (MSE) and coefficient of determination (R2) were exercised to choose the best regression model. Correlation results indicated a high positive significant correlation (P < 0.01) among BW and RH (r = 0.69), BL (r = 0.92), HG (r = 0.91), WH (r = 0.85) in bucks. While it does, all the linear body measurements indicated a high positive significant correlation (P < 0.01) expect SH (r = 0.41) which had a positive significant correlation (P < 0.05). Simple linear regression findings highlighted that BL had minimum MSE and highest R2 in bucks while in does HG had minimum MSE and highest R2. PCR-RFLP results indicated that two fragment patterns (two fragments and one fragment) were identified. Two genotypes were identified, KK with one fragment and KM with two fragments. The genotype frequency of KK was higher than that of KM and K allele had a higher allelic frequency than the M allele. The χ2 results showed that the Kalahari Red goats population used was not in Hardy Weinberg equilibrium (HWE) (χ2 = 0.39*). Marker-trait association findings by GLM indicated that the genotypes (KK and KM) had no association with the growth traits measured. In conclusion, correlation findings suggest that BW had a higher relationship with BL and HG in Kalahari Red goats. The regression results suggest that in bucks, an increase of 1 cm of BL might increase body weight by 1.24 kg, whereas it does, a 1 cm increase of HG might increase the body weight by 0.73 kg. The χ2 results suggest that the studied population gene and genotypic frequencies keep on changing from generation to generation and the marker-traits association results suggest that the genotypes identified had no relationship with growth traits in Kalahari Red goats. Further studies need to be conducted on single nucleotide polymorphism of IGF-1 and their relationship with growth traits using a larger sample, more growth traits and targeting more exons. / National Research Foundation (NRF)

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Τα αυξημένα επίπεδα εμβρυϊκής αιμοσφαιρίνης (HbF) μετριάζουν την βαρύτητα των διαταραχών που αφορούν στην β-σφαιρίνη, δηλαδή τη δρεπανοκυτταρική αναιμία (SCD) και την β-μεσογειακή αναιμία, που αποτελούν σημαντικές αιτίες παγκόσμιας νοσηρότητας και θνησιμότητας. Γι’ αυτό το λόγο είναι μακροχρόνιο το ενδιαφέρον για την ανάπτυξη θεραπευτικών προσεγγίσεων για την επαγωγή της παραγωγής HbF. Η αναζήτηση μορίων που ρυθμίζουν την μετάβαση από την έκφραση της εμβρυϊκής (HbF) στην έκφραση της αιμοσφαιρίνης των ενηλίκων (HbA) και που συντελούν στην διατήρηση της αποσιώπησης ή αντίθετα στην ενεργοποίηση της έκφρασης της HbF στους ανθρώπους αποτελεί πολυετές αντικείμενο έρευνας με σκοπό την στόχευση αυτών των παραγόντων για την επαγωγή της HbF (Sankaran et al. 2011). Έτσι, εκτός από τα cis-ρυθμιστικά στοιχεία, έχουν εντοπιστεί και trans-ρυθμιστικά στοιχεία, τα οποία αποτελούν κυρίως μεταγραφικούς παράγοντες. Όμως υπάρχουν και γονιδιακοί τόποι εκτός του β-συμπλέγματος που φαίνεται να επιδούν στην ρύθμιση της έκφρασης των γονιδίων του β-γονιδιακού τόπου. Τέτοιοι είναι οι τόποι που συνδέονται με «ποσοτικά γνωρίσματα» (Quantitative trait loci-QTL). Η χρωμοσωμική περιοχή 6q23 έχει σε διάφορες μελέτες προσδιοριστεί ως QTL, που συνδέεται με την μεταβολή των επιπέδων της HbF σε ασθενείς με SCD. (Close et al. 2004, Thein et al. 2007, Wyszynski et al. 2004). Ο σκοπός της παρούσας μελέτης είναι διττός: A. Ο εντοπισμός μονονουκλεοτιδικών πολυμορφισμών (SNP) εντός των γονιδίων MAP3K5 και PDE7B του QTL στην 6q23 χρωμοσωμική περιοχή, που να σχετίζονται με αυξημένα επίπεδα HbF. B. Η αξιολόγηση των SNP αυτών ως φαρμακογονιδιωματικών δεικτών, που να σχετίζονται με την μεταβλητότητα των επιπέδων της HbF ως απόκριση στη θεραπεία με HU. / Hemoglobinopathies, particularly β-thalassemia and sickle cell disease (SCD), are major health problems, in which quantitative or qualitative defects in hemoglobin production occur, respectively. Under normal circumstances, different types of hemoglobin (Hb) are produced during embryonic, fetal, and adult life. At birth, fetal hemoglobin (HbF), in particular, composes 80–90% of the total hemoglobin synthesized, but it gradually decreases to approximately 1% by 10 months in infancy as its synthesis is restricted to a small subset of erythrocytes termed ‘F cells’ [Patrinos&Grosveld, 2008]. The first studies searching for regulators of HbF expression were conducted on individuals with heterocellular hereditary persistence of HbF (HPFH) – i.e. increase of HbF levels unevenly distributed among ‘F cells’ – and suggested the absence of linkage between the determinant of the HbF levels and the β-globin gene cluster, back then named “non-α globin cluster” [Gianni et al., 1983]. Later, while seeking for genetic elements associated with elevated HbF levels in healthy adults, several cis-acting variants on the β-globin gene complex were unraveled, including the XmnI-Gγ (HBG2) gene promoter polymorphism [Gilman et al., 1985]. Ιn addition, variants unlinked to the β-locus (trans-acting), such as quantitative trait loci (QTLs) on Xp22 [Dover et al., 1992] and 6q23 [Craig et al., 1996] became known soon after. Initially, a study on an extensive, inbred kindred of Asian Indian origin with heterocellular HPFH revealed that a key locus controlling HPFH resides on chromosome 6q, which was fine-mapped to 6q22.3–23.1 [Craig et al., 1996]. Among the first positional candidate genes in the 6q23 region, assumed to possibly explain this QTL, were the MYB proto-oncogene and the eukaryotic release factor-similar HBS1L, as well as the mitogen-activated protein kinase kinase kinase 5 (MAP3K5) [Game et al., 2000]. In addition, genes within this region are associated with response to hydroxyurea (HU) treatment based on elevated HbF levels, in SCD patients; however, the mechanism by which this chromosome 6q22-23 QTL influences HbF levels in the context of HU treatment remains unknown [Ma et al., 2007] and very few, if any, studies have addressed this question. In continuing the global effort of scrutinizing the 6q23 region for variants accounting for the modulation of HbF production, we investigated a possible association of SNPs residing within the MAP3K5 and PDE7B genes with elevated HbF levels in β-thalassemia intermediate or major patients and normal (non-thalassemic) individuals. We also examined a cohort of 38 heterozygous SCD/β-thalassemia patients who had undergone HU therapy, in order to clarify whether there is a correlation of these SNPs with HU treatment response in patients of Hellenic origin.

A nefropatia diabética (ND) é uma das principais causas de nefropatia crônica, o que torna o diabetes mellitus (DM) responsável por 44% da prevalência de doença renal crônica (DRC) no mundo. O papel do estresse oxidativo na patogênese da ND está bem estabelecido e genes pertencentes a vias pró- e antioxidantes são possíveis candidatos a conferirem susceptibilidade genética a essa e a outras complicações crônicas. Além do estresse oxidativo, o transporte intracelular de glicose, mediado por transportadores específicos, também parece exercer influência sobre a ND e outras complicações. O objetivo deste trabalho foi avaliar a associação entre ND e alguns polimorfismos de um único nucleotídeo (SNPs) em genes que codificam proteínas transportadoras de glicose (GLUT2 [SLC2A2]), proteínas pró-oxidantes (p22phox [CYBA] e NOX-2 [CYBB]) e proteínas antioxidantes (glutationa peroxidase-4 [GPX4] e catalase [CAT]) em uma coorte brasileira (n=453; 45,8% de pacientes com ND) e três coortes francesas (SURGENE [n=340; 17,7% de pacientes com ND na fase basal], GENEDIAB [n=313; 66,7% de pacientes com ND] e GENESIS [n=636; 49,7% de pacientes com ND]) de pacientes portadores de DM tipo 1. Os SNPs foram genotipados com o uso da técnica de reação em cadeia da polimerase (PCR) em tempo real e os resultados expressos em odds ratio (OR) ou hazard ratio (HR), com seus respectivos intervalos de confiança (IC), determinados em modelos ajustados de regressão logística politômica ou regressão de risco proporcional de Cox, respectivamente. A razão albumina/creatinina urinária (ACR) ou a taxa de excreção urinária de albumina (EUA) foram utilizadas para definir os estágios de ND e os pacientes foram classificados de acordo com a presença ou ausência de ND incipiente (ACR 30 - 300 mg/g de creatinina ou EUA 20 - 200 ?g/min ou 20 - 200 mg/L) e creatinina plasmática <1,7 mg/dL), ND estabilizada (ACR >300 mg/g de creatinina ou EUA > 200 ug/min ou > 200 mg/L e creatinina plasmática < 1,7 mg/dL ) ou ND avançada (ACR > 300 mg/g de creatinina ou EUA > 200 ug/min ou > 200 mg/L e creatinina plasmática > 1,7 mg/dL ou qualquer terapia de reposição renal) e também foram avaliadas associações dos SNPs com a taxa de filtração glomerular estimada (TFGe). O alelo raro A do SNP rs6610650 no gene CYBB foi associado com valores baixos de TFGe em mulheres na coorte brasileira e com a prevalência de ND estabilizada/avançada em mulheres da coorte francesa (OR 1,75; IC 95% 1,11 - 2,78; p=0,016). O alelo raro T do SNP rs713041 no gene GPX4 foi inversamente associado com a prevalência de ND estabilizada/avançada em homens na coorte brasileira (OR 0,30, IC95% 0,13 - 0,68, p=0,004) e com valores elevados de TFGe em homens na coorte francesa. O alelo raro A do SNP rs7947841 no gene CAT foi associado com a prevalência de ND incipiente (OR 2,79; IC95% 1,21 - 6,24; p=0,01) e ND estabilizada/avançada (OR 5,72; IC95% 1,62 - 22,03; p=0,007), bem como com a incidência de eventos renais, definidos como novos casos de microalbuminúria ou progressão para um estágio mais grave de ND durante o seguimento de estudo, na coorte SURGENE (HR 1,82; IC95% 1,13 - 2,81; p=0,01). O mesmo alelo de risco associou-se com a prevalência de ND incipiente (OR 3,13; IC95% 1,42 - 7,24; p=0,004) e com a incidência de insuficiência renal crônica terminal (IRCT) na coorte GENEDIAB (HR 2,11; IC95% 1,23 - 3,60; p=0,008) e com a prevalência de ND incipiente (OR 2,16; IC95% 1,14 - 4,10, p=0,02) e ND estabilizada/avançada (OR 2,71; IC95% 1,38 - 5,42; p=0,004) na coorte brasileira. O alelo raro T do SNP rs9932581 no gene CYBA foi inversamente associado com a prevalência de ND estabilizada/avançada (OR 0,60; IC95% 0,46 - 0,78; p=0,0001) e com valores mais baixos de TFGe nos pacientes de descendência europeia da coorte GENESIS/GENEDIAB. Este mesmo alelo foi associado com a incidência de eventos renais e de IRCT nas coortes SURGENE (HR 0,63; IC95% 0,46 - 0,86; p=0,003) e GENESIS/GENEDIAB (HR 0,51; IC95% 0,31 - 0,78; p=0,002), respectivamente. Entretanto estes resultados não foram replicados na coorte brasileira. O alelo raro T do SNP rs11924032 no gene SLC2A2 foi inversamente associado com a perda da TFGe ao logo do tempo (0,02%/ano vs 2,18%/ano para os pacientes portadores do genótipo GG; p=0,005), na coorte SURGENE. Este mesmo alelo foi inversamente associado com a incidência de IRCT nas coortes GENESIS/GENEDIAB (HR 0,53; IC95% 0,29 - 0,89; p=0,01). Os resultados observados para o gene SLC2A2 não forneceram fortes indícios para afirmarmos que este gene exerça um papel relevante no desenvolvimento da ND nos pacientes com DM tipo 1 nas coortes francesas estudadas. Em contrapartida, os SNPs nos genes que codificam as proteínas pró-oxidantes CYBA e CYBB e as proteínas antioxidantes GPX-4 e CAT foram capazes de modular o risco para doença renal em pacientes portadores de DM tipo 1, sendo que os SNPs presentes nos genes CYBB, GPX4 e CAT tiveram seus resultados replicados em coortes independentes, o que corrobora a importância destes genes e, consequentemente, do estresse oxidativo, na patogênese da ND / Diabetic nephropathy (DN) is a major cause of chronic nephropathy, with diabetes mellitus (DM) accounting for 44% of the prevalence of chronic kidney disease (CKD) in the world. The role of oxidative stress in the pathogenesis of DN is well established and genes belonging to pro- and antioxidant pathways are possible candidates to confer genetic susceptibility to this and other chronic complications. Besides oxidative stress, intracellular glucose transport mediated by specific transporters, also appears to influence DN and other complications. The aim of this study was to evaluate the association between DN and some single nucleotide polymorphisms (SNPs) present in genes encoding glucose transport proteins (GLUT2 [SLC2A2]), pro- (p22phox [CYBA] and NOX-2 [CYBB]) and antioxidants (glutathione peroxidase-4 [GPX4] and catalase [CAT]) proteins, in a Brazilian cohort [n= 453; 45.8% f patients with DN], and three French cohorts (SURGENE [n=340; 17.7% of patients with DN at baseline], GENEDIAB [n=313; 66.7% of patients with DN], and GENESIS [n=636; 49.7% of patients with DN]) of patients with type 1 DM. The SNPs were genotyped using the technique of real time polymerase chain reaction (PCR) and results expressed as odds ratio (OR) and hazard ratio (HR), with their respectively 95% confidence intervals (CI), determined by adjusted models of polytomic logistic regression and Cox proportional hazard regression, respectively. The albumin/creatinine ratio (ACR) or the urinary albumin excretion (UAE) rate were used to define the DN stages and the patients were classified according to the presence or absence of incipient DN (ACR 30 - 300 mg/g of creatinine or UAE 20 - 200 ug/min or 20 - 200 mg/L) and plasmatic creatinine < 1,7 mg/dL), established DN (ACR > 300 mg/g of creatinine or EUA > 200 ug/min or > 200 mg/L and plasmatic creatinine <1,7 mg/dL) or advanced DN (ACR >300 mg/g of creatinine or UAE > 200 ug/min or > 200 mg/L and plasmatic creatinine > 1,7 mg/dL or any renal replacement therapy). Associations for the estimated glomerular filtration rate (eGFR) were also evaluated. The rare allele A of the SNP rs6610650 in CYBB gene was associated with low values of eGFR in women in the Brazilian cohort and with the prevalence of established/advanced DN in women in the French cohort (OR 1.75, 95%CI 1.11 - 2.78, p=0.016). The rare allele T of the SNP rs713041 in GPX4 gene was inversely associated with the prevalence of established/advanced DN in men in the Brazilian cohort (OR 0.30, 95%CI 0.13 - 0.68, p=0.004) and with higher values of eGFR in men in the French cohort. The rare allele A of the SNP rs7947841 in CAT gene was associated with the prevalence of incipient DN (OR 2.79, 95%CI 1.21 - 6.24, p=0.01) and established/advanced DN (OR 5.72; 95%CI 1.62 - 22.03, p=0.007) as well as the incidence of renal events, defined as new cases of microalbuminuria or progression to a more severe stage during the follow-up study, in SURGENE cohort (HR 1.82, 95%CI 1.13 - 2.81, p=0.01). The same risk allele was associated with the prevalence of incipient DN (OR 3.13, 95%CI 1.42 - 7.24, p=0.004), the incidence of end-stage renal disease (ESRD) in the cohort GENEDIAB (HR 2.11, 95%CI 1.23 - 3.60, p=0.008) and with the prevalence of incipient DN (OR 2.16, 95%CI 1.14 - 4.10, p=0.02) and established/advanced DN (OR 2.71, 95%CI 1.38 - 5.42, p=0.004) in the Brazilian cohort. The rare T allele of the SNP rs9932581 in CYBA gene was inversely associated with the prevalence of established/advanced DN (OR: 0.60, 95%CI: 0.46 - .78, p=0.0001) and associated with lower values of eGFR in patients of GENESIS/GENEDIAB cohort. The same allele was inversely associated with the incidence of renal events and ESRD in SURGENE (HR 0.63, 95%CI 0.46 - 0.86, p=0.003) and GENESIS/GENEDIAB (HR 0.51, 95%CI 0.31 - 0.78, p=0.002) cohorts. However, these results were not replicated in the Brazilian cohort. The rare T allele of the SNP rs11924032 in SLC2A2 gene was inversely associated with the loss of eGFR during the follow-up (0.02%/year vs. 2.18%/year for patients with the GG genotype, p=0.005) in the SURGENE cohort. The same allele was inversely associated with the incidence of ESRD in the GENESIS/GENEDIAB cohorts (HR 0.53, 95%CI 0.29 - 0.89, p=0.01). The results observed for the SLC2A2 gene, in this study, did not provide strong evidence to state that this gene exerts a relevant role in the development of DN in patients with type 1 DM in the studied cohorts. However, SNPs in genes encoding the pro-oxidant proteins CYBA and CYBB, and the antioxidants proteins GPX-4 and CAT were able to modulate the risk of renal disease in patients with type 1 DM. The studied SNPs in CYBB, GPX4 and CAT genes had their results replicated in independent cohorts, which confirms the importance of these genes and, hence, of the oxidative stress in the pathogenesis of DN

Species conservation is typically founded upon a range of management strategies, which integrate both biological and socioeconomic data. In this thesis, population genetics, acoustic telemetry, spawning aggregation surveys and stakeholder assessments were used to address key knowledge gaps limiting effective conservation management for critically endangered Nassau grouper (Epinephelus striatus) stocks in The Bahamas. A panel of polymorphic microsatellite markers was optimised to assess the genetic population dynamics of more than 400 Nassau grouper sampled throughout the country. Microsatellite data indicate that contemporary Nassau grouper populations in The Bahamas are predominantly genetically diverse and weakly differentiated, but lack geographic population structure. Assessments of changes in effective population size (Ne) show substantive reductions in Ne within The Bahamas compared to historic values that are likely due to natural disturbances. Evidence for recent bottlenecks occurring in three islands as well as an active spawning site, along with higher inbreeding coefficients in two islands were also found, and can be attributed to more recent anthropogenic activities. Collapse of a historically important Nassau grouper fish spawning aggregation (FSA) was supported by both acoustic telemetry and spawning aggregation survey dives. Restriction-site-associated DNA sequencing (RAD-seq) of 94 Nassau grouper was used to explore intraspecific population dynamics, loci under selection and patterns of gene flow in The Bahamas. Genomic assessments of diversity were in accord with microsatellite data and examinations of gene flow support higher levels of connectivity in The Bahamas than was previously suggested. The increased resolution gained from assessments of genomic data support intraspecific population structuring that may be driven by differences in gene flow and putative loci under divergent selection. Telemetry data were successfully used to identify the origins of spawning adults, and support demographic connectivity through migrations between an active FSA in the central Bahamas and home reef habitats within the Exumas and a no-take marine protected area. Stakeholder assessments highlight the complexities of fisheries management within The Bahamas, with key stakeholders often exhibiting conflicting opinions regarding the status of Nassau grouper and the efficacy of management options. However, these groups mutually agree upon the need to better manage remaining Nassau grouper stocks within The Bahamas through science-grounded policies. Synthesis of these studies along with a review of fisheries governance in The Bahamas was used to develop a comprehensive national management plan for Nassau grouper to facilitate better conservation for remaining populations of this ecologically important marine species.

Para avaliar a influência dos polimorfismos de nucleotídeo único (SNPs) do CYP2B6, CYP3A5, GSTM1, GSTP1, GSTT1, PON1, NQO1 e MDR1 na resposta ao tratamento com R-CHOP e CHOP, 82 pacientes com Linfoma Difuso de Grandes Células B, sem evidências de infecção por HIV, foram selecionados nesse estudo. Amostras de sangue periférico foram coletadas para extração de DNA. Os SNPs foram analisados por PCR-RFLP. Em relação aos pacientes que apresentaram resposta completa (RC) ao tratamento (70%), 51% foram tratados com R-CHOP. Sobre o tratamento, 50% dos pacientes com RC apresentaram classificação de ECOG 0-1 (p=0,0193) e a maioria desses pacientes (41%) não apresentaram envolvimento extranodal (p=0,0377). Não houve associação entre os SNPs do CYP2B6, CYP3A5, GSTT1, NQO1 e MDR1 (C3435T) e as variáveis estudadas. Apenas CYP3A5 (sexo p=0,0519), GSTM1 (idade p=0,016; tratamento p=0,0372), GSTP1 (envolvimento extranodal p=0,0307), PON1 (sintomas B p=0,0201; Bulky p=0,0148) e MDR1 C1236T (sexo p=0,0316) mostraram associação. Em relação à sobrevida global, apenas tratamento (p=0,0129), IPI (p=0,000342), idade (p=0,0155), estadiamento (p=0,00281) e ECOG (p=0,00869) apresentaram resultados significantes. Quanto à sobrevida livre de doença (SLD), apenas idade (p=0,0292), estadiamento (p=0,0402) e ECOG (p=0,0142) apresentaram resultados significantes / To evaluated the influence of single nucleotide polymorphisms (SNPs) of CYP2B6, CYP3A5, GSTM1, GSTP1, GSTT1, PON1, NQO1 and MDR1 in the treatment response with R-CHOP and CHOP, 82 patients with Diffuse Large B-cell Lymphoma, without evidence of HIV infection, were enrolled in this study. Peripheral blood samples were collected for DNA extraction. The SNPs were analyzed by PCR-RFLP. In relation the patients that showed complete response (CR) to the treatment (70%), 51% were treated with R-CHOP. About the treatment, 50% of the patients with CR showed ECOG classification of 0-1 and the most of these patients (41%) did not showed extranodal involvement (p=0,0377). There was no association between CYP2B6, CYP3A5, GSTT1, NQO1 and MDR1 (C3435T) SNPs and the variables studied. Only CYP3A5 (gender p=0,0519), GSTM1 (age p=0,016; treatment p=0,0372), GSTP1 (extranodal involvement p=0,0307), PON1 (B symptoms p=0,0201; Bulky p=0,0148) e MDR1 C1236T (gender p=0,0316) showed association. In relation to overall survival, only treatment (p=0,0129), IPI (p=0,000342), age (p=0,0155), stadiament (p=0,00281) and ECOG (p=0,00869) showed significant results. To disease-free survival, only age (p=0,0292), stadiament (p=0,0402) e ECOG (p=0,0142) showed significant results