Association of Single Nucleotide Polymorphisms on Locus 18q21.1 in the Etiology of Nonsyndromic Cleft Lip Palate (NSCLP) in Indian Multiplex Families.

Cleft lip palate (CLP) is a common congenital anomaly with multifactorial etiology. Many polymorphisms at different loci on multiple chromosomes were reported to be involved in its etiology. Genetic research on a single multigenerational American family reported 18q21.1 locus as a high-risk locus for nonsyndromic CLP (NSCLP). However, its association in multiple multiplex families and Indian population is not analyzed for its association in NSCLP.  This study was aimed to evaluate whether high-risk single nucleotide polymorphisms (SNPs) on chromosome 18q21.1 are involved in the etiology of NSCLP in multiplex Indian families.  Twenty multigenerational families affected by NSCLP were selected for the study after following inclusion and exclusion criteria. Genomic DNA was isolated from the affected and unaffected members of these 20 multiplex families and sent for genetic analysis. High-risk polymorphisms, such as rs6507872 and rs8091995 of , rs17715416, rs17713847 and rs183559995 of , rs78950893 of , rs1450425 of , and rs6507992 of candidate genes on the 18q21.1 locus, were analyzed. SNP genotyping was done using the MassARRAY method. Statistical analysis of the genomic data was done by PLINK.  Polymorphisms followed the Hardy-Weinberg equilibrium. In the allelic association, all the polymorphisms had a -value more than 0.05. The odds ratio was not more than 1.6 for all the SNPs.  High-risk polymorphisms, such as rs6507872 and rs8091995 of , rs17715416, rs17713847 and rs183559995 of , rs78950893 of , rs1450425 of , and rs6507992 of in the locus 18q21.1, are not associated with NSCLP in Indian multiplex families.