Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines

Abstract

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia

“…Importantly, the portion of tryptase activity due to α/β-tryptase increases with the α-tryptase gene dosage. Consequently, an α-tryptase genedosage effect associated with a particular clinical phenotype, as shown in the current study for a cutaneous response to vibration or as reported for severe Dengue infection (Velasquez et al, 2015) or asthma (Abdelmotelb et al, 2014), might implicate involvement of α/β-tryptase. Also, as α-tryptase gene deficiency varies among individuals with Asian, European, and African backgrounds (Trivedi et al, 2009), affecting α/β-tryptase content, a role for these heterotetramers can now be considered in the context of natural selection.…”

Trends in dengue research in the Philippines: A systematic review

“…We removed 77 duplicates and screened the titles and abstracts of 759 articles, of which 624 (82%) were excluded and 135 (18%) full text articles were downloaded and reviewed. The 135 articles were classified as follows: 44 (33%) descriptive epidemiologic studies or case series [8–51], 21 (16%) entomologic or vector control studies [52–72], 16 (12%) studies on dengue virology and serologic response [73–88], 13 (10%) socio-behavioral and economics studies [89–101], 11 (8%) clinical trials [102–112], 10 (7%) on burden of disease [113–122], 10 (7%) investigations on markers of disease severity [123–132], 7 (5%) on dengue diagnostics [133–139], and 3 (2%) modeling studies [140–142]. The majority (102/135, 76%) of the dengue research locations were in Metro Manila.…”

“…Ten studies looked for associations between biomarkers and clinical presentation of dengue disease. Eight studies assessed levels of various immune-related or enzymatic biomarkers [123–127, 130–132], while two evaluated the potential role of adiposity [128, 129]. More research is needed to better understand the host characteristics that contribute to dengue disease severity.…”

Relationship Between Urbanization and Dengue Hemorrhagic Fever Incidence in Semarang City

“…This statement is collaborated by the results of several study (Conroy et al, 2015;Devaleenal et al, 2015;Murugananthan et al, 2014;Phung et al, 2015;Vasquez-Velasquez et al, 2015), which stated that the adverse effects of the phenomenon of urbanization form the ideal environment for the aedes aegypti mosquito as a carrier vector for breeding in the urban settlement area .…”