Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations

Ji Wan Park, Iain McIntosh, Jacqueline B. Hetmanski, Ethylin Wang Jabs, Craig A. Vander Kolk, Yah Huei Wu-Chou, Philip K. Chen, Samuel S. Chong, Vincent Yeow, Sun Ha Jee, Beyoung Yun Park, M. Daniele Fallin, Roxann Ingersoll, Alan F. Scott, Terri H. Beaty

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. RESULTS: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10 and P = 5 × 10, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalGenetics in Medicine
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 1 2007
Externally publishedYes

Fingerprint

Interferon Regulatory Factors
Cleft Lip
Cleft Palate
Palate
Population
Single Nucleotide Polymorphism
Logistic Models
Genes
Genetic Counseling
Ethnic Groups
Haplotypes
Genotype

Keywords

  • Association
  • Ethnicity
  • Interferon regulatory factor 6
  • Oral cleft
  • Risk estimation
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Park, J. W., McIntosh, I., Hetmanski, J. B., Jabs, E. W., Vander Kolk, C. A., Wu-Chou, Y. H., ... Beaty, T. H. (2007). Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. Genetics in Medicine, 9(4), 219-227. https://doi.org/10.1097/GIM.0b013e3180423cca

Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. / Park, Ji Wan; McIntosh, Iain; Hetmanski, Jacqueline B.; Jabs, Ethylin Wang; Vander Kolk, Craig A.; Wu-Chou, Yah Huei; Chen, Philip K.; Chong, Samuel S.; Yeow, Vincent; Jee, Sun Ha; Park, Beyoung Yun; Fallin, M. Daniele; Ingersoll, Roxann; Scott, Alan F.; Beaty, Terri H.

In: Genetics in Medicine, Vol. 9, No. 4, 01.04.2007, p. 219-227.

Research output: Contribution to journalArticle

Park, JW, McIntosh, I, Hetmanski, JB, Jabs, EW, Vander Kolk, CA, Wu-Chou, YH, Chen, PK, Chong, SS, Yeow, V, Jee, SH, Park, BY, Fallin, MD, Ingersoll, R, Scott, AF & Beaty, TH 2007, 'Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations', Genetics in Medicine, vol. 9, no. 4, pp. 219-227. https://doi.org/10.1097/GIM.0b013e3180423cca
Park, Ji Wan ; McIntosh, Iain ; Hetmanski, Jacqueline B. ; Jabs, Ethylin Wang ; Vander Kolk, Craig A. ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Chong, Samuel S. ; Yeow, Vincent ; Jee, Sun Ha ; Park, Beyoung Yun ; Fallin, M. Daniele ; Ingersoll, Roxann ; Scott, Alan F. ; Beaty, Terri H. / Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. In: Genetics in Medicine. 2007 ; Vol. 9, No. 4. pp. 219-227.
@article{490e74993a0c4af4a3ba6f4adea2d5ac,
title = "Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations",
abstract = "PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. RESULTS: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10 and P = 5 × 10, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.",
keywords = "Association, Ethnicity, Interferon regulatory factor 6, Oral cleft, Risk estimation, Single nucleotide polymorphism",
author = "Park, {Ji Wan} and Iain McIntosh and Hetmanski, {Jacqueline B.} and Jabs, {Ethylin Wang} and {Vander Kolk}, {Craig A.} and Wu-Chou, {Yah Huei} and Chen, {Philip K.} and Chong, {Samuel S.} and Vincent Yeow and Jee, {Sun Ha} and Park, {Beyoung Yun} and Fallin, {M. Daniele} and Roxann Ingersoll and Scott, {Alan F.} and Beaty, {Terri H.}",
year = "2007",
month = "4",
day = "1",
doi = "10.1097/GIM.0b013e3180423cca",
language = "English",
volume = "9",
pages = "219--227",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations

AU - Park, Ji Wan

AU - McIntosh, Iain

AU - Hetmanski, Jacqueline B.

AU - Jabs, Ethylin Wang

AU - Vander Kolk, Craig A.

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Chong, Samuel S.

AU - Yeow, Vincent

AU - Jee, Sun Ha

AU - Park, Beyoung Yun

AU - Fallin, M. Daniele

AU - Ingersoll, Roxann

AU - Scott, Alan F.

AU - Beaty, Terri H.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. RESULTS: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10 and P = 5 × 10, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.

AB - PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. RESULTS: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10 and P = 5 × 10, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.

KW - Association

KW - Ethnicity

KW - Interferon regulatory factor 6

KW - Oral cleft

KW - Risk estimation

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=34247273084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247273084&partnerID=8YFLogxK

U2 - 10.1097/GIM.0b013e3180423cca

DO - 10.1097/GIM.0b013e3180423cca

M3 - Article

C2 - 17438386

AN - SCOPUS:34247273084

VL - 9

SP - 219

EP - 227

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 4

ER -