Dataset Information

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

ABSTRACT: 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.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.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.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.ISRCTN ISRCTN03147572 . Registered 24th July 2012.

SUBMITTER: Whitehorn J

PROVIDER: S-EPMC5466782 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Whitehorn James J Kien Duong Thi Hue DTH Quyen Nguyen Than Ha NTH Wills Bridget B Van Vinh Chau Nguyen N Tam Dong Thi Hoai DTH Tuan Nguyen Minh NM Jaenisch Thomas T Hibberd Martin M Khor Chiea Chuen CC Simmons Cameron P CP

BMC infectious diseases 20170609 1

<h4>Background</h4>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.<h4>Methods</h4>This w ...[more]

PMID: 28599625

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Project description:BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64), when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ? 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.

Dataset Information

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

Publications

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

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