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Résumé Une mutation des deux allèles du gène Rb durant le développement rétinien normal est responsable de l’apparition du rétinoblastome. La recherche de mutations au niveau du gène Rb reste difficile, car la majorité des altérations sont uniques et dispersées tout au long du gène. Nous rapportons dans notre étude le résultat de l’analyse du gène Rb au niveau constitutionnel et tumoral dans la population algérienne. Notre étude a porté sur un échantillon de 21 patients atteints de rétinoblastome. Le promoteur et les 27 exons avec leurs séquences introniques flanquantes composant le gène Rb ont été amplifiés et analysés par HPLC (chromatographie liquide à haute performance) suivie d’un séquençage. Les variations de bases identifiées au niveau constitutionnel et tumoral sont au nombre de 7 dont 3 mutations non sens, une mutation affectant le site d’épissage, une délétion et 2 polymorphismes. L’analyse du gène Rb a été réalisée chez des enfants atteints de rétinoblastome ne présentant aucun antécédent familial de la maladie. Par cette étude, nous avons pu identifier deux cas sur les 21 étudiés ayant un rétinoblastome pouvant être transmissible. Deux mutations rapportées n’ont jamais été décrites dans la littérature. Articles originaux Journal de la Faculté de Médecine d’Oran Jfmo Article original Abstract Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutional and tumoral RB1 analysis in an Algerian population. The detection of RB1 gene deletion or mutation was performed by high performance liquid chromatography (HPLC) and sequence analyses in 21 patients.Germline abnormalities were found in 2/21 patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included 3 nonsense mutations, 1 mutation affecting splice site, 1 deletion and 2 polymorphisms. In general, for the 21 patients with no family history of the disease we have identified mutations in germinal level in two of them showing that it is a transmissible form of retinoblastoma in these two cases known to be sporadic. A total of 2 mutations have not been previously reported.

Résumé Introduction - Le gène TP53 a fait l’objet de très nombreux travaux. Sa nature polymorphe et son rôle central dans la régulation du cycle cellulaire ont mis en évidence son potentiel de gène candidat dans la susceptibilité et la survenue de différents cancers. Bien que plusieurs polymorphismes du gène TP53 aient été étudiés comme facteurs de risque pour différents cancers, le plus largement étudié est le polymorphisme Arg72Pro (rs1042522), à l’origine d’une substitution d’une Arginie (Arg) en Proline (Pro) ou inversement, connu pour ses différentes fonctions biologiques. Notre objectif est d’explorer la participation du polymorphisme (SNP) Arg72Pro du gène TP53, dans l’expressivité du cancer colorectal (CCR) et du carcinome basocellulaire (CBC) dans une population de l’Ouest Algérien. Matériels et Méthodes - Le déséquilibre de transmission allélique de ce SNP a été réalisé sur une population constituée de 116 individus atteints de CCR, 50 sujets atteints de CBC et enfin une population contrôle constituée de 121 individus sains, par la technique de Biologie Moléculaire PCR/RFLP (Polymerase Chain Reaction/ Restriction Fragment LengthPolymorphism). Résultats - L’association du marqueur Arg72Pro avec le CBC a montré une augmentation significative de l’allèle Pro chez les cas par rapport aux contrôles (54% vs 46%, OR=8,85 [4,98-16,03], p0.05). Conclusion - Le polymorphisme Arg72Pro du gène TP53 peut être considéré comme marqueur de risque pour le CBC mais pas pour le CCR. Abstract Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy, reaching one out of every 5000 male births in the world population. It is characterized by progressive muscular degeneration from a young age and leads to serious failures of the body which lead to the death of the patient. The gene responsible for DMD is located on chromosome X. It encodes a membrane cytoskeleton protein»the dystrophin». The alterations affecting this gene are essentially deletions with a proportion of 65%. That’s why we have interested to develop in our laboratory a technique that will allow us to detect this type of mutations in 5 sporadic cases with Duchenne myopathy from West Algeria. The study consisted in amplifying by PCR multiplex that cover 19 exons of the DMD gene most commonly deleted. This study allowed us to reveal two different deletions, the first involving the promoter of the gene and the second one the exon 43. These first results confirm the data reported in the literature which classify these two regions as deletion hotspots. The results obtained represent a first in the western Algerian and could lead to the generalization of genotypic diagnosis and genetic counseling with a view to improve the care of patients in Algeria.

Résumé Objectif - L’accumulation des variants génétiques participe au processus impliqué dans le risque de développer le cancer colorectal (CCR). Plusieurs études ont exploré la corrélation entre les polymorphismes 6986A>G du gène CYP3A5 (CYP450) (rs776746) appartenant à la famille des cytochromes P450 et 3435C>T du gène adénosine triphosphate–binding cassette B1 (ABCB1) (rs1045642). L’objectif de cette étude est la recherche d’éventuelles associations entre les polymorphismes rs776746 et rs1045642, et la survenue du cancer colorectal dans une population de l’Ouest Algérien. Méthodes - La cohorte était composée de 99 patients atteints de CCR et 101 contrôles. Les polymorphismes CYP3A5 c.6986A>G et ABCB1 c.3435 >T ont été identifiés par la technique de discrimination allélique par PCR quantitative en temps réel. Les résultats ont été analysés par le calcul de l’odd ratio (OR) avec un intervalle de confiance à 95%. Résultats - L’étude cas-témoins a montré que la distribution des fréquences alléliques et génotypiques de ces polymorphismes entre les deux groupes (cas et témoins) ne présentait aucune différence statistiquement significative. Conclusion - Ce travail nous a permis de conclure qu’il n’existait aucune relation d’association entre ces polymorphismes et la survenue du CCR dans notre population. Abstract Objective - The accumulation of genetic variants participates in the process involved in the risk of developing colorectal cancer (CRC). Several studies have explored the correlation between the 6986A> G polymorphisms of the CYP3A5 (CYP450) gene (rs776746) belonging to the cytochrome P450 and 3435C> T family of the adenosine triphosphate-binding cassette B1 (ABCB1) gene (rs1045642). The objective of this study is to investigate a possible association of rs776746 and rs1045642 polymorphisms with the occurrence of colorectal cancer on a population of western Algeria. Methods - The cohort consisted of 99 CRC patients and 101 controls. The CYP3A5 c.6986A> G and ABCB1 c.3435> T polymorphisms were identified by the allelic discrimination by quantitative real-time PCR technique. The results were analyzed by calculating the odd ratio (OR) with a 95% confidence interval. Results - This case-control study didn’t show any statistically significant difference in allelic and genotypic frequencies of these polymorphisms between the two groups (case and control). Conclusion - This work allowed us to conclude that there was no association between these polymorphisms and the occurrence of CRC in our population.

Résumé Objectif - En Algérie, le cancer de la prostate (CP) représente un réel problème de santé publique. Notre étude consiste à déterminer l’influence du polymorphisme Thr241Met du gène XRCC3 sur la susceptibilité à développer le CP. Pour cela, nous avons entrepris une étude d’association cas/témoins portant sur ce polymorphisme dans un échantillon de la population de l’Ouest Algérien. Matériels et méthodes - Cette étude a concerné dix sujets atteints de CP et vingt sujets sains non apparentés. L’exploration des différents génotypes du polymorphisme a été réalisée par la technique d’amplification en chaine par polymérase - polymorphisme de longueur des fragments de restriction (PCR-RFLP). La comparaison des fréquences alléliques et génotypiques entre les deux groupes à été établie par le calcul de l’odds ratio (OR) avec un intervalle de confiance à 95%. Résultats - A ce stade de l’étude, l’analyse statistique a montré qu’il n’existait aucune différence statistiquement significative de distribution des fréquences alléliques et génotypiques (OR=0,36 [0,12-1,1] ;P=0,7) de ce polymorphisme exploré entre les cas et les contrôles dans ce premier échantillon de la population explorée. Conclusion - En conclusion, il est envisagé d’augmenter le nombre de cas à étudier pour confirmer cette absence d’association. Par ailleurs, il est important d’explorer d’autres polymorphismes situés non seulement sur le gène XRCC3 mais aussi sur d’autres gènes impliqués dans la réparation de l’ADN, afin de caractériser au mieux sur le plan génétique, le cancer de la prostate dans la population de l’Ouest Algérien. Abstract Objective - In Algeria, prostate cancer (PC) is a real public health problem. Our study consists in determining the influence of the polymorphism Thr241Met of the XRCC3 gene on the susceptibility to develop a PC. To this end, we undertook a case-control study of this polymorphism in a sample of the Algerian West population. Materials and methods - This case-control study involved 10 subjects with PC and 20 unrelated healthy subjects. The various genotypes of the polymorphism were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The comparison of allelic and genotypic frequencies between the two groups was established by calculating the odds ratio (OR) with a 95% confidence interval. Results - In this preliminary exploration, statistical analysis showed that there was no statistically significant difference in the distribution of allelic and genotypic frequencies (OR = 0.36 [0.12-1.1], P = 0.7) of the polymorphism explored between cases and controls in this first sample of the population explored. Conclusion - In conclusion, we consider increasing the size of the sample to be studied to confirm this lack of association. On the other hand, we believe that it is important to explore other polymorphisms located not only on the XRCC3 gene but also on other genes involved in DNA repair in order to enhance genetic characterization of PC in the western Algerian population.

Abstract Objectives - The aim of this study is to determine the impact of the gamma glutamyl hydrolase (GGH) c.452C>T (dbSNP Id: rs 11545078) polymorphism on the Methotrexate (MTX) adverse drug reactions (ADRs) and on MTX gastro intestinal toxicity (GIT) in rheumatoid arthritis (RA) patients. Materials and methods - Sixty-one patients with RA are enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Data were analyzed by χ2. Results - Our findings suggest that the frequencies distributions of alleles/genotypes of this polymorphism were similar in both groups with and without ADRs. However, there is a significant distribution of GGH 452TT (p=0.03) and GGH 452CT+452TT (p=0.02) genotypes between the groups with and without GIT. The same correlation was found for GGH 452T allele (p=0.008). Conclusion - We have shown for the first time in the West Algerian population that the GGH c.452C>T polymorphism influences the MTX gastro-intestinal toxicity

Objective - In Algeria, prostate cancer (PC) is a real public health problem. Our study consists in determining the influence of the polymorphism Thr241Met of the XRCC3 gene on the susceptibility to develop a PC. To this end, we undertook a case-control study of this polymorphism in a sample of the Algerian West population. Materials and methods - This case-control study involved 10 subjects with PC and 20 unrelated healthy subjects. The various genotypes of the polymorphism were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The comparison of allelic and genotypic frequencies between the two groups was established by calculating the odds ratio (OR) with a 95% confidence interval. Results - In this preliminary exploration, statistical analysis showed that there was no statistically significant difference in the distribution of allelic and genotypic frequencies (OR = 0.36 [0.12-1.1], P = 0.7) of the polymorphism explored between cases and controls in this first sample of the population explored. Conclusion - In conclusion, we consider increasing the size of the sample to be studied to confirm this lack of association. On the other hand, we believe that it is important to explore other polymorphisms located not only on the XRCC3 gene but also on other genes involved in DNA repair in order to enhance genetic characterization of PC in the western Algerian population.

Abstract Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutional and tumoral RB1 analysis in an Algerian population. The detection of RB1 gene deletion or mutation was performed by high performance liquid chromatography (HPLC) and sequence analyses in 21 patients.Germline abnormalities were found in 2/21 patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included 3 nonsense mutations, 1 mutation affecting splice site, 1 deletion and 2 polymorphisms. In general, for the 21 patients with no family history of the disease we have identified mutations in germinal level in two of them showing that it is a transmissible form of retinoblastoma in these two cases known to be sporadic. A total of 2 mutations have not been previously reported.

Objectives - The aim of this study is to determine the impact of the gamma glutamyl hydrolase (GGH) c.452C>T (dbSNP Id: rs 11545078) polymorphism on the Methotrexate (MTX) adverse drug reactions (ADRs) and on MTX gastro intestinal toxicity (GIT) in rheumatoid arthritis (RA) patients. Materials and methods - Sixty-one patients with RA are enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Data were analyzed by χ2. Results - Our findings suggest that the frequencies distributions of alleles/genotypes of this polymorphism were similar in both groups with and without ADRs. However, there is a significant distribution of GGH 452TT (p=0.03) and GGH 452CT+452TT (p=0.02) genotypes between the groups with and without GIT. The same correlation was found for GGH 452T allele (p=0.008). Conclusion - We have shown for the first time in the West Algerian population that the GGH c.452C>T polymorphism influences the MTX gastro-intestinal toxicity.

Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy, reaching one out of every 5000 male births in the world population. It is characterized by progressive muscular degeneration from a young age and leads to serious failures of the body which lead to the death of the patient. The gene responsible for DMD is located on chromosome X. It encodes a membrane cytoskeleton protein»the dystrophin». The alterations affecting this gene are essentially deletions with a proportion of 65%. That’s why we have interested to develop in our laboratory a technique that will allow us to detect this type of mutations in 5 sporadic cases with Duchenne myopathy from West Algeria. The study consisted in amplifying by PCR multiplex that cover 19 exons of the DMD gene most commonly deleted. This study allowed us to reveal two different deletions, the first involving the promoter of the gene and the second one the exon 43. These first results confirm the data reported in the literature which classify these two regions as deletion hotspots. The results obtained represent a first in the western Algerian and could lead to the generalization of genotypic diagnosis and genetic counseling with a view to improve the care of patients in Algeria.

Résumé La Dystrophie Musculaire de Duchenne (DMD) est la plus sévère et la plus fréquente des dystrophies musculaires, atteignant une naissance mâle sur 5000 dans la popu­lation mondiale. Elle se caractérise par une dégénérescence musculaire progressive dès le jeune âge et conduit à des défaillances graves de l’organisme qui aboutissent au décès du patient. Le gène responsable de la DMD est localisé sur le chromosome X. Il code pour une protéine du cytosquelette membranaire « la dystrophine ». Les altérations touchant ce gène sont essentiellement des délétions avec une proportion de 65%. C’est la rai­son pour laquelle nous nous sommes intéressés à la mise au point au niveau de notre laboratoire d’une technique qui nous permettra de mettre en évidence ce type de mutation chez 5 cas sporadiques atteints de myopathie de Duchenne et originaires de l’Ouest Algérien. L’étude a consisté à amplifier par PCR multiplex les 19 exons du gène DMD les plus fréquemment altérés. Cette étude nous a permis de mettre en évidence deux délétions différentes, la pre­mière touchant le promoteur du gène et la seconde l’exon 43. Ces premiers résultats confirment les données rapportées dans la littérature qui classent ces deux régions comme étant les régions les plus disposées aux délétions. Les résultats obtenus représentent une première au niveau de l’ouest algérien et pourraient aboutir à la généralisation du diagnostic génotypique et du conseil géné­tique en vue d’une amélioration de la prise en charge des malades en Algérie. Abstract Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscu­lar dystrophy, reaching one out of every 5000 male births in the world population. It is characterized by progressive muscular degeneration from a young age and leads to serious failures of the body which lead to the death of the patient. The gene responsible for DMD is located on chromosome X. It encodes a membrane cytoskeleton protein»the dystrophin». The alterations affecting this gene are essen­tially deletions with a proportion of 65%. That’s why we have interested to develop in our laboratory a technique that will allow us to detect this type of mutations in 5 sporadic cases with Duchenne myopathy from West Algeria. The study consisted in amplifying by PCR multiplex that cover 19 exons of the DMD gene most commonly deleted. This study allowed us to reveal two different deletions, the first involving the pro­moter of the gene and the second one the exon 43. These first results confirm the data reported in the literature which classify these two regions as deletion hotspots. The results obtained represent a first in the western Algerian and could lead to the generalization of genotypic diagnosis and genetic counseling with a view to improve the care of patients in Algeria.

Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy, reaching one out of every 5000 male births in the world population. It is characterized by progressive muscular degeneration from a young age and leads to serious failures of the body which lead to the death of the patient. The gene responsible for DMD is located on chromosome X. It encodes a membrane cytoskeleton protein»the dystrophin». The alterations affecting this gene are essentially deletions with a proportion of 65%. That’s why we have interested to develop in our laboratory a technique that will allow us to detect this type of mutations in 5 sporadic cases with Duchenne myopathy from West Algeria. The study consisted in amplifying by PCR multiplex that cover 19 exons of the DMD gene most commonly deleted. This study allowed us to reveal two different deletions, the first involving the promoter of the gene and the second one the exon 43. These first results confirm the data reported in the literature which classify these two regions as deletion hotspots. The results obtained represent a first in the western Algerian and could lead to the generalization of genotypic diagnosis and genetic counseling with a view to improve the care of patients in Algeria.

Objective - The accumulation of genetic variants participates in the process involved in the risk of developing colorectal cancer (CRC). Several studies have explored the correlation between the 6986A> G polymorphisms of the CYP3A5 (CYP450) gene (rs776746) belonging to the cytochrome P450 and 3435C> T family of the adenosine triphosphate-binding cassette B1 (ABCB1) gene (rs1045642). The objective of this study is to investigate a possible association of rs776746 and rs1045642 polymorphisms with the occurrence of colorectal cancer on a population of western Algeria. Methods - The cohort consisted of 99 CRC patients and 101 controls. The CYP3A5 c.6986A> G and ABCB1 c.3435> T polymorphisms were identified by the allelic discrimination by quantitative real-time PCR technique. The results were analyzed by calculating the odd ratio (OR) with a 95% confidence interval. Results - This case-control study didn’t show any statistically significant difference in allelic and genotypic frequencies of these polymorphisms between the two groups (case and control). Conclusion - This work allowed us to conclude that there was no association between these polymorphisms and the occurrence of CRC in our population.