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BMC Infect Dis. 2017 Jun 9;17(1):412. doi: 10.1186/s12879-017-2514-6.

Genetic variants of MICB and PLCE1 and associations with the laboratory features of dengue.

Author information

1
Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK. james.whitehorn@lshtm.ac.uk.
2
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Viet Nam. james.whitehorn@lshtm.ac.uk.
3
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Viet Nam.
4
Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
5
Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Viet Nam.
6
Children Hospital Number 1, Ho Chi Minh City, Viet Nam.
7
Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
8
Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
9
Genome Institute of Singapore, Biopolis Way, Singapore, Singapore.
10
School of Public Health, National University of Singapore, Singapore, Singapore.
11
Department of Paediatrics, National University of Singapore, Singapore, Singapore.
12
Department of Ophthalmology, National University of Singapore, Singapore, Singapore.
13
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute, Melbourne, VIC, 3010, Australia.

Abstract

BACKGROUND:

A previous genome-wide association study identified 2 susceptibility loci for severe dengue at MICB rs3132468 and PLCE1 rs3740360 and further work showed these mutations to be also associated with less severe clinical presentations. The aim of this study was to determine if these specific loci were associated with laboratory features of dengue that correlate with clinical severity with the aim of elucidating the functional basis of these genetic variants.

METHODS:

This was a case-only analysis of laboratory-confirmed dengue patients obtained from 2 prospective cohort studies and 1 randomised clinical trial in Vietnam (Trial registration: ISRCTN ISRCTN03147572. Registered 24th July 2012). 2742 dengue cases were successfully genotyped at MICB rs3132468 and PLCE1 rs3740360. Laboratory variables were compared between genotypes and stratified by DENV serotype.

RESULTS:

The analysis showed no association between MICB and PLCE1 genotype and early viraemia level, platelet nadir, white cell count nadir, or maximum haematocrit in both overall analysis and in analysis stratified by serotype.

DISCUSSION:

The lack of an association between genotype and viremia level may reflect the sampling procedures within the included studies. The study findings mean that the functional basis of these mutations remains unclear.

TRIAL REGISTRATION:

ISRCTN ISRCTN03147572 . Registered 24th July 2012.

PMID:
28599625
PMCID:
PMC5466782
DOI:
10.1186/s12879-017-2514-6
[Indexed for MEDLINE]
Free PMC Article

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