A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1 in Thai patients with dengue shock syndrome

BMC Medical Genetics

Jun Ohashi²  Naoyuki Tsuchiya²  Jintana Patarapotikul⁴  Pathom Sawanpanyalert¹  Nuanjun Wichukchinda³  Sumalee Chanama³  Surapee Anantapreecha³  Areerat Sa-Ngasang³  Izumi Naka²  Tran Ngoc Dang² 

[1] Food and drug Administration, Ministry of Public Heath, Nonthaburi, Thailand;Faculty of Medicine, University of Tsukuba, Tsukuba, Japan;Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand;Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

关键词: Polymorphism;    PLCE1;    MICB;    Expression;    Dengue shock syndrome (DSS);    Association;   

Others  :  1091716
DOI  :  10.1186/1471-2350-15-58

 received in 2014-02-02, accepted in 2014-05-12,  发布年份 2014

【 摘 要 】

Background

Dengue shock syndrome (DSS), a severe life-threatening form of dengue infection, mostly occurs in children. A recent genome wide association study (GWAS) identified two SNPs, rs3132468 of major histocompatibility complex class I polypeptide-related sequence B (MICB) and rs3765524 of phospholipase C, epsilon 1 (PLCE1), associated with DSS in Vietnamese children. In this study, to examine whether an identical association is found in a different population, the association of these two SNPs with DSS was assessed in Thai children with dengue.

Methods

The rs3132468 and rs3765524 SNPs were genotyped in 917 Thai children with dengue: 76 patients with DSS and 841 patients with non-DSS. The allele frequencies were compared between DSS and non-DSS groups by one-sided Fisher’s exact test. The association of rs3132468 and rs3765524 with the mRNA expression levels of MICB and PLCE1 were assessed in EBV-transformed lymphoblastoid cell lines.

Results

The reported DSS-risk alleles were significantly associated with DSS in Thai patients with dengue (one-sided P = 0.0213 and odds ratio [OR] = 1.58 for rs3132468-C and one-sided P = 0.0252 and OR = 1.49 for rs3765524-C). The rs3132468-C allele showed a significant association with lower mRNA level of MICB (P = 0.0267), whereas the rs3765524-C allele did not. These results imply that the MICB molecule may play an important role in the prevention of DSS in dengue infection.

Conclusions

Together with previous association studies, we conclude that rs3132468-C at MICB and rs3765524-C at PLCE1 confer risk of DSS in Southeast Asians.

【 授权许可】

   
2014 Dang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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