title: Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia.
abstract: Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.
authors: Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia. Electronic address: hbpeng@salam.uitm.edu.my.
authors: B P
authors: BP
authors: Hoh
authors: Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: H
authors: H
authors: Umi-Shakina
authors: Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: Z
authors: Z
authors: Zuraihan
authors: Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: M Z
authors: MZ
authors: Zaiharina
authors: Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors: S
authors: S
authors: Rafidah-Hanim
authors: Department of Medicine, Hospital Kota Bharu, Kota Bharu, Kelantan, Malaysia.
authors: M
authors: M
authors: Mahiran
authors: Department of Paediatrics, Hospital Kota Bharu, Kota Bharu, Kelantan, Malaysia.
authors: N Y Nik
authors: NY
authors: Khairudin
authors: Department of Medicine, Hospital Sungai Buloh, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: L H Sim
authors: LH
authors: Benedict
authors: Department of Medicine, Hospital Sungai Buloh, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: Z
authors: Z
authors: Masliza
authors: Department of Medicine, Hospital Sungai Buloh, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors: K C Lee
authors: KC
authors: Christopher
authors: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; Tropical Infectious Disease Research and Education Centre, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: A B
authors: AB
authors: Sazaly
mesh_terms: D000328:Adult; D000483:Alleles; D002199:Capillary Permeability; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000276:immunology; D054371:Chemokine CXCL11 / Q000235:genetics* / Q000276:immunology; D003715:Dengue / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008024:Ligands; D008296:Malaysia; D008297:Male; D054367:Receptors, CXCR3 / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D008024:Ligands; D054367:Receptors, CXCR3
keywords: CXCL10; CXCL11; CXCR3; Common variant; Dengue; Genetic association; Vascular permeability