The association between interferon regulatory factor 6 (IRF6) and nonsyndromic cleft lip with or without cleft palate in a Honduran population.
OBJECTIVE
Interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome (VWS), is a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) because a number of studies have supported an association between NSCLP and single nucleotide polymorphisms (SNPs) in IRF6 in several populations. This project investigated the contribution of IRF6 to NSCLP in the Honduran population, a previously unstudied group with a high prevalence of NSCLP.


METHODS
Family-based joint linkage and association study.


METHODS
A set of five SNPs in and around IRF6 previously reported to be associated with NSCLP were tested for association with NSCLP in 276 affected and unaffected Honduran individuals from 59 families with at least two members affected by clefting and at least one member with confirmed NSCLP.


RESULTS
We observed support of linkage for three SNPs-rs1856161, rs2235371, and rs2235377-under a dominant model (log of odds [LODs] = 1.97, 1.56, 1.73, respectively). Subsequent single-point, haplotype, and joint linkage and association analyses continued to support the association with NSCLP (P < or = .05) at these three SNPs. When analysis was restricted to NSCLP cases, excluding cleft palate only cases, support for association strengthened.


CONCLUSIONS
This is the first study to demonstrate that three candidate SNPs within IRF6 are significantly associated with NSCLP in the Honduran population, providing the first genetic clue to NSCLP observed in the Honduran population and confirming findings from populations in other parts of the world. Further studies are needed to identify the putative variant(s).
Diercks
Gillian R
GR
Columbia University College of Physicians and Surgeons, New York, New York, USA.
Karnezis
Tom T
TT
Kent
David T
DT
Flores
Carlos
C
Su
Gloria H
GH
Lee
Joseph H
JH
Haddad
Joseph
J
D002971:Cleft Lip / Q000150:complications / Q000235:genetics*; D002972:Cleft Palate / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006721:Honduras; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors