Susceptible and protective HLA class 1 alleles against dengue fever and dengue hemorrhagic fever patients in a Malaysian population

• Published in: PloS one 2010-09, Vol.5 (9), p.e13029
• Main Authors: Appanna, Ramapraba, Ponnampalavanar, Sasheela, Lum Chai See, Lucy, Sekaran, Shamala Devi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Case-Control Studies; Dengue - epidemiology; Dengue - genetics; Dengue - immunology; Dengue - virology; Dengue fever; Dengue hemorrhagic fever; Dengue virus; Dengue Virus - genetics; Dengue Virus - isolation & purification; Dengue Virus - physiology; Development and progression; Disease control; Disease susceptibility; Epidemics; Female; Fever; Genetic aspects; Genetic markers; Genetic polymorphisms; Genetic Predisposition to Disease; Genotype; Health aspects; Histocompatibility antigen HLA; HLA antigens; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Humans; Immunity, Innate; Immunology/Genetics of the Immune System; Infection; Infections; Infectious Diseases/Neglected Tropical Diseases; Infectious Diseases/Viral Infections; Leukocytes; Malaysia - epidemiology; Male; Medical research; Microbiology/Immunity to Infections; Middle Aged; Minority & ethnic groups; Patients; Polymerase chain reaction; Population genetics; Public Health and Epidemiology/Infectious Diseases; Severe Dengue - epidemiology; Severe Dengue - genetics; Severe Dengue - immunology; Severe Dengue - virology; Vector-borne diseases; Viral diseases; Viral infections; Virology/Effects of Virus Infection on Host Gene Expression; Virology/Emerging Viral Diseases; Virology/Host Antiviral Responses; Viruses; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013029

The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia. This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian) in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008) allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19-23.02) and B*18 (P = 0.017, Pc = 0.408) alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03-0.90) was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576) was seen to be negatively associated with DHF. These are the first findings on genetic polymorphisms in our population and we conclude that: (1) In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2) In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine.