Combined genetic effects of RET and NRG1 susceptibility variants on multifactorial Hirschsprung disease in Indonesia

Gunadi; Kristy Iskandar; Akhmad Makhmudi; Ashish Kapoor

doi:10.1016/j.jss.2018.07.067

Combined genetic effects of RET and NRG1 susceptibility variants on multifactorial Hirschsprung disease in Indonesia

Gunadi, Kristy Iskandar, Akhmad Makhmudi, Ashish Kapoor

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Specific genetic variants at RET (rs2435357) and NRG1 (rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect of RET rs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry. Methods: Sixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped for RET rs2506030 using the TaqMan assay. Results: RET rs2506030 was associated with HSCR both by case-control analysis (odds ratio = 1.68; P = 0.043) and the transmission disequilibrium test (P = 0.034). Furthermore, individuals with five or six risk alleles at RET rs2506030, rs2435357 and NRG1 rs7835688 showed ∼45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles. Conclusions: Disease risk of HSCR is increased by the combination of specific RET and NRG1 susceptibility variants.

Original language	English (US)
Pages (from-to)	96-99
Number of pages	4
Journal	Journal of Surgical Research
Volume	233
DOIs	https://doi.org/10.1016/j.jss.2018.07.067
State	Published - Jan 2019
Externally published	Yes

Keywords

Combined effect
Common variants
Hirschsprung disease
Indonesia
NRG1
RET

ASJC Scopus subject areas

Surgery

Access to Document

10.1016/j.jss.2018.07.067

Cite this

@article{8e519dfc8d26473582ca06091c95cbad,

title = "Combined genetic effects of RET and NRG1 susceptibility variants on multifactorial Hirschsprung disease in Indonesia",

abstract = "Background: Specific genetic variants at RET (rs2435357) and NRG1 (rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect of RET rs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry. Methods: Sixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped for RET rs2506030 using the TaqMan assay. Results: RET rs2506030 was associated with HSCR both by case-control analysis (odds ratio = 1.68; P = 0.043) and the transmission disequilibrium test (P = 0.034). Furthermore, individuals with five or six risk alleles at RET rs2506030, rs2435357 and NRG1 rs7835688 showed ∼45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles. Conclusions: Disease risk of HSCR is increased by the combination of specific RET and NRG1 susceptibility variants.",

keywords = "Combined effect, Common variants, Hirschsprung disease, Indonesia, NRG1, RET",

author = "Gunadi and Kristy Iskandar and Akhmad Makhmudi and Ashish Kapoor",

note = "Funding Information: The studies were supported by the grant from the Indonesian Ministry of Research, Technology and Higher Education and Fulbright (“DIKTI-Fulbright Senior Research Fellowship 2013” to G.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = jan,

doi = "10.1016/j.jss.2018.07.067",

language = "English (US)",

volume = "233",

pages = "96--99",

journal = "Journal of Surgical Research",

issn = "0022-4804",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Combined genetic effects of RET and NRG1 susceptibility variants on multifactorial Hirschsprung disease in Indonesia

AU - Gunadi,

AU - Iskandar, Kristy

AU - Makhmudi, Akhmad

AU - Kapoor, Ashish

N1 - Funding Information: The studies were supported by the grant from the Indonesian Ministry of Research, Technology and Higher Education and Fulbright (“DIKTI-Fulbright Senior Research Fellowship 2013” to G.). Publisher Copyright: © 2018 Elsevier Inc.

PY - 2019/1

Y1 - 2019/1

N2 - Background: Specific genetic variants at RET (rs2435357) and NRG1 (rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect of RET rs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry. Methods: Sixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped for RET rs2506030 using the TaqMan assay. Results: RET rs2506030 was associated with HSCR both by case-control analysis (odds ratio = 1.68; P = 0.043) and the transmission disequilibrium test (P = 0.034). Furthermore, individuals with five or six risk alleles at RET rs2506030, rs2435357 and NRG1 rs7835688 showed ∼45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles. Conclusions: Disease risk of HSCR is increased by the combination of specific RET and NRG1 susceptibility variants.

AB - Background: Specific genetic variants at RET (rs2435357) and NRG1 (rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect of RET rs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry. Methods: Sixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped for RET rs2506030 using the TaqMan assay. Results: RET rs2506030 was associated with HSCR both by case-control analysis (odds ratio = 1.68; P = 0.043) and the transmission disequilibrium test (P = 0.034). Furthermore, individuals with five or six risk alleles at RET rs2506030, rs2435357 and NRG1 rs7835688 showed ∼45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles. Conclusions: Disease risk of HSCR is increased by the combination of specific RET and NRG1 susceptibility variants.

KW - Combined effect

KW - Common variants

KW - Hirschsprung disease

KW - Indonesia

KW - NRG1

KW - RET

UR - http://www.scopus.com/inward/record.url?scp=85051680133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051680133&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2018.07.067

DO - 10.1016/j.jss.2018.07.067

M3 - Article

C2 - 30502294

AN - SCOPUS:85051680133

SN - 0022-4804

VL - 233

SP - 96

EP - 99

JO - Journal of Surgical Research

JF - Journal of Surgical Research

ER -

Combined genetic effects of RET and NRG1 susceptibility variants on multifactorial Hirschsprung disease in Indonesia

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this