Fethi Mecabih1, Fatiha Sadouki2, Meriem Bennabi3, Sofiane Salah1, Wahid Boukouaci3, Habiba Amroun4, Catherine Fortier5, François Marzais5, Dominique Charron6, Hachemi Djoudi2, Mohamed Cherif Abbadi4, Rajagopal Krishnamoorthy3, Ryad Tamouza7. 1. Laboratoire de Transplantation et d'Immunogénétique, Département d'Immunologie, Institut Pasteur d'Algérie, Alger 16000, Algeria; INSERM, UMRS 1160, Hôpital Saint Louis, Paris 75010, France. 2. Service de Rhumatologie, Etablissement Hospitalier Spécialisé de Douera, Alger 16000, Algeria. 3. INSERM, UMRS 1160, Hôpital Saint Louis, Paris 75010, France. 4. Laboratoire de Transplantation et d'Immunogénétique, Département d'Immunologie, Institut Pasteur d'Algérie, Alger 16000, Algeria. 5. Laboratoire Jean Dausset et LabEx Transplantex, Hôpital Saint Louis, Paris 75010, France. 6. Laboratoire Jean Dausset et LabEx Transplantex, Hôpital Saint Louis, Paris 75010, France; Université Paris Diderot, Sorbonne Paris-Cité, Paris 75013, France. 7. INSERM, UMRS 1160, Hôpital Saint Louis, Paris 75010, France; Laboratoire Jean Dausset et LabEx Transplantex, Hôpital Saint Louis, Paris 75010, France; Université Paris Diderot, Sorbonne Paris-Cité, Paris 75013, France. Electronic address: tamouza.ryad@gmail.com.
Abstract
OBJECTIVE: Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), a key player in immune-mediated responses against Mycobacterium tuberculosis, is encoded by a polymorphic gene. Functionally relevant polymorphic variations in the MCP-1 gene have been associated with both susceptibility to and protection against tuberculosis-related disorders. Here, we investigated the potential impact of some of these polymorphisms on Pott's disease risk in a patient cohort from Algeria. METHODS: DNA from 132 Algerian patients with exclusive Pott's disease and 204 healthy controls, included under a case-control design, were analyzed for the MCP1 -2518A/G (rs1024611), -362G/C (rs2857656) and int1del554-567 (rs3917887) polymorphisms. PHASE software was used for haplotype reconstruction. Genetic associations were examined using chi-square tests. RESULTS: We found that the rs1024611 -2518 GG, rs2857656 -362 CC and rs3917887 int1del554-567 del/del homozygous genotypes each were significantly more prevalent in patients than in controls (respective corrected p value [Pc]=0.01, 0.04 and 0.04) Haplotype distribution profile further confirmed this, as the homozygous combination of GCdel haplotype was also found with raised susceptibility to Pott's disease (Pc=0.03). CONCLUSION: Our findings confirm and replicate the recent data from China (which dealt essentially with rs1024611 and rs2857656) and also reinforce them by providing trans-ethnic evidence and extending the genetic association to the rs3917887.
OBJECTIVE:Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), a key player in immune-mediated responses against Mycobacterium tuberculosis, is encoded by a polymorphic gene. Functionally relevant polymorphic variations in the MCP-1 gene have been associated with both susceptibility to and protection against tuberculosis-related disorders. Here, we investigated the potential impact of some of these polymorphisms on Pott's disease risk in a patient cohort from Algeria. METHODS: DNA from 132 Algerian patients with exclusive Pott's disease and 204 healthy controls, included under a case-control design, were analyzed for the MCP1 -2518A/G (rs1024611), -362G/C (rs2857656) and int1del554-567 (rs3917887) polymorphisms. PHASE software was used for haplotype reconstruction. Genetic associations were examined using chi-square tests. RESULTS: We found that the rs1024611 -2518 GG, rs2857656 -362 CC and rs3917887 int1del554-567 del/del homozygous genotypes each were significantly more prevalent in patients than in controls (respective corrected p value [Pc]=0.01, 0.04 and 0.04) Haplotype distribution profile further confirmed this, as the homozygous combination of GCdel haplotype was also found with raised susceptibility to Pott's disease (Pc=0.03). CONCLUSION: Our findings confirm and replicate the recent data from China (which dealt essentially with rs1024611 and rs2857656) and also reinforce them by providing trans-ethnic evidence and extending the genetic association to the rs3917887.
Authors: Bart N Green; Claire D Johnson; Scott Haldeman; Erin Griffith; Michael B Clay; Edward J Kane; Juan M Castellote; Shanmuganathan Rajasekaran; Matthew Smuck; Eric L Hurwitz; Kristi Randhawa; Hainan Yu; Margareta Nordin Journal: PLoS One Date: 2018-06-01 Impact factor: 3.240