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BMC Medical Genetics

, 12:170

First Online: 21 December 2011Received: 23 September 2011Accepted: 21 December 2011

Abstract

BackgroundRecent genome-wide association studies GWAS for asthma have been successful in identifying novel associations which have been well replicated. The aim of this study is to identify the genetic variants that influence predisposition towards asthma in an ethnic Chinese population in Singapore using a GWAS approach.

MethodsA two-stage GWAS was performed in case samples with allergic asthma, and in control samples without asthma and atopy. In the discovery stage, 490 case and 490 control samples were analysed by pooled genotyping. Significant associations from the first stage were evaluated in a replication cohort of 521 case and 524 control samples in the second stage. The same 980 samples used in the discovery phase were also individually genotyped for purposes of a combined analysis. An additional 1445 non-asthmatic atopic control samples were also genotyped.

Results19 promising SNPs which passed our genome-wide P value threshold of 5.52 × 10 were individually genotyped. In the combined analysis of 1011 case and 1014 control samples, SNP rs2941504 in PERLD1 on chromosome 17q12 was found to be significantly associated with asthma at the genotypic level P = 1.48 × 10, ORAG = 0.526 0.369-0.700, ORAA = 0.480 0.361-0.639 and at the allelic level P = 9.56 × 10, OR = 0.745 0.654-0.848. These findings were found to be replicated in 3 other asthma GWAS studies, thus validating our own results. Analysis against the atopy control samples suggested that the SNP was associated with allergic asthma and not to either the asthma or allergy components. Genotyping of additional SNPs in 100 kb flanking rs2941504 further confirmed that the association was indeed to PERLD1. PERLD1 is involved in the modification of the glycosylphosphatidylinositol anchors for cell surface markers such as CD48 and CD59 which are known to play multiple roles in T-cell activation and proliferation.

ConclusionsThese findings reveal the association of a PERLD1 as a novel asthma candidate gene and reinforce the involvement of genes on the 17q12-21 chromosomal region in the etiology of asthma.

Abbreviations usedACE angiotensin I converting enzyme

C5 complement component 5

CCL11 chemokine C-C motif ligand 11

CCL2 chemokine C-C motif ligand 2

CCL5 chemokine C-C motif ligand 5

CD2 Cluster of differentiation 2

CD48 Cluster of differentiation 48

CD59 Cluster of differentiation 59

CHI3L1 chitinase 3-like 1

DENND1B DENN-MADD domain containing 1B

DPP10 dipeptidyl-peptidase 10

ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2

GPI glycosylphosphatidylinositol

GPI-AP glycosylphosphatidylinositol-anchored protein

GSDMB gasdermin B

GWAS genome-wide association study

HLA human leukocyte antigen

HLA-DQB1 major histocompatibility complex, class II, DQ beta 1

IL18R1 interleukin 18 receptor 1

IL1RL1 interleukin 1 receptor-like 1

ITGB3 integrin beta 3

MHC major histocompatibility complex

ORMDL3 ORM1-like 3

PDE4D phosphodiesterase 4D

PERLD1 Per1-like domain containing 1

RAD50 RAD50 homolog

SNP single nucleotide polymorphism

STARD3 StAR-related lipid transfer START domain containing 3

TGFB1 transforming growth factor beta 1.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-170 contains supplementary material, which is available to authorized users.

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Autor: Ramani Anantharaman - Anand Kumar Andiappan - Pallavi Parate Nilkanth - Bani Kaur Suri - De Yun Wang - Fook Tim Chew

Fuente: https://link.springer.com/



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