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Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever.

ABSTRACT: Dengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue.A previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet count in healthy subjects. To examine the possible association of these SNPs with DHF, 918 Thai patients with dengue [509 patients with DHF and 409 with dengue fever (DF)] were genotyped for five SNPs: rs5745568 in BAK1, rs6141 in THPO, rs6065 in GP1BA, rs739496 in SH2B3, and rs385893 in RCL1. In addition, rs4804803 in CD209, that has been reported to be associated with dengue infection, was also genotyped to examine if rs4804803 affects the association detected in this study.The allele frequencies of each SNP were compared between the DHF and DF groups. Among the five SNPs, the G allele of rs5745568 in BAK1 was significantly associated with a risk for DHF [P?=?0.006 and crude odd ratio (95 % confidence interval)?=?1.32 (1.09-1.60)]. The association of this allele with DHF was also significant in a logistic regression analysis adjusted for age, sex, hospital (i.e., geographic region), immune status (i.e., primary or secondary infection), and virus serotype [P?=?0.016 and adjusted odd ratio (95 % confidence interval)?=?1.29 (1.05-1.58)]. The result was not influenced by rs4804803 [P?=?0.0167 and adjusted OR (95 % CI)?=?1.29 (1.05-1.58)]. No other SNPs including rs4804803 showed significant association.The low-level constitutive production of platelets caused by the G allele of rs5745568 seems to increase the risk of bleeding in dengue infection. Our results suggest that BCL-2 homologous antagonist/killer (BAK) protein, encoded by BAK1, plays a crucial role in the pathogenesis of DHF.

SUBMITTER: Dang TN

PROVIDER: S-EPMC4940700 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever.

Dang Tran Ngoc TN Naka Izumi I Sa-Ngasang Areerat A Anantapreecha Surapee S Wichukchinda Nuanjun N Sawanpanyalert Pathom P Patarapotikul Jintana J Tsuchiya Naoyuki N Ohashi Jun J

BMC medical genetics 20160711 1

<h4>Background</h4>Dengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue.<h4>Methods</h4>A previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet co ...[more]

PMID: 27401010

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Project description:BACKGROUND:The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. METHODS:A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. RESULTS:A total 667 dengue patients (30.69?±?16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P?<?0.05) associated with DHF than DF. Multivariate regression analysis demonstrated presence of age?>?40 years (OR: 4.1, P?<?0.001), secondary infection (OR: 2.7, P?=?0.042), diabetes mellitus (OR: 2.8, P?=?0.041), lethargy (OR: 3.1, P?=?0.005), thick gallbladder (OR: 1.7, P?=?0.029) and delayed hospitalization (OR: 2.3, P?=?0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. CONCLUSIONS:Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.

Project description:BackgroundIncreased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors.MethodsA total of 208 Thai subjects, aged 35-75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated.ResultsArterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype.ConclusionsOur findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.

Dataset Information

Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever.

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Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever.

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