A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1 in Thai patients with dengue shock syndrome
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 phos...
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Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
2014
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Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/760 |
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Institution: | Mahidol University |
Language: | English |
Summary: | 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. |
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