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

Abstract

Background 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.

Aim 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.

Materials and Methods 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 CTIF, rs17715416, rs17713847 and rs183559995 of MYO5B, rs78950893 of SMAD7, rs1450425 of LOXHD1, and rs6507992 of SKA1 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.

Results Polymorphisms followed the Hardy–Weinberg equilibrium. In the allelic association, all the polymorphisms had a p-value more than 0.05. The odds ratio was not more than 1.6 for all the SNPs.

Conclusion High-risk polymorphisms, such as rs6507872 and rs8091995 of CTIF, rs17715416, rs17713847 and rs183559995 of MYO5B, rs78950893 of SMAD7, rs1450425 of LOXHD1, and rs6507992 of SKA1 in the locus 18q21.1, are not associated with NSCLP in Indian multiplex families.

Keywords

cleft lip palate - chromosome - SNP

Publikationsverlauf

Artikel online veröffentlicht:
19. Februar 2021

• References

• 1 Mossey P. Global strategies to reduce the healthcare burden of craniofacial anomalies. Br Dent J 2003; 195 (10) 613-13
• 2 Reddy SG, Reddy RR, Bronkhorst EM. et al. Incidence of cleft lip and palate in the state of Andhra Pradesh, South India. Indian J Plast Surg 2010; 43 (02) 184-189
• 3 Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 2011; 12 (03) 167-178
• 4 Neela P, Reddy S, Husain A, Mohan V. Association of cleft lip and/or palate in people born to consanguineous parents: a 13-year retrospective study from a very high-volume cleft center. J Cleft Lip Palate Craniofacial Anomalies 2019; 6: 33-37
• 5 Mossey P, Little J. Addressing the challenges of cleft lip and palate research in India. Indian J Plast Surg 2009; 42 (suppl): S9-S18
• 6 Leslie EJ, Taub MA, Liu H. et al. Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci. Am J Hum Genet 2015; 96 (03) 397-411
• 7 Mehrotra D. Genomic expression in non syndromic cleft lip and palate patients: A review. J Oral Biol Craniofac Res 2015; 5 (02) 86-91
• 8 Vieira AR. Unraveling human cleft lip and palate research. J Dent Res 2008; 87 (02) 119-125
• 9 Sull JW, Liang KY, Hetmanski JB. et al. Differential parental transmission of markers in RUNX2 among cleft case-parent trios from four populations. Genet Epidemiol 2008; 32 (06) 505-512
• 10 Funato N, Nakamura M. Identification of shared and unique gene families associated with oral clefts. Int J Oral Sci 2017; 9 (02) 104-109
• 11 Beiraghi S, Nath SK, Gaines M. et al. Autosomal dominant nonsyndromic cleft lip and palate: significant evidence of linkage at 18q21.1. Am J Hum Genet 2007; 81 (01) 180-188
• 12 Mitra AK, Stessman HA, Schaefer RJ. et al. Fine-mapping of 18q21.1 locus identifies single nucleotide polymorphisms associated with nonsyndromic cleft lip with or without cleft palate. Front Genet 2016; 7: 88
• 13 Hong EP, Park JW. Sample size and statistical power calculation in genetic association studies. Genomics Inform 2012; 10 (02) 117-122
• 14 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16 (03) 1215
• 15 Purcell S, Neale B, Todd-Brown K. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81 (03) 559-575
• 16 Radhakrishna U, Ratnamala U, Gaines M. et al. Genomewide scan for nonsyndromic cleft lip and palate in multigenerational Indian families reveals significant evidence of linkage at 13q33.1-34. Am J Hum Genet 2006; 79 (03) 580-585
• 17 Hao J, Gao R, Wu W. et al. Association between BMP4 gene polymorphisms and cleft lip with or without cleft palate in a population from South China. Arch Oral Biol 2018; 93: 95-99
• 18 Rafighdoost H, Hashemi M, Danesh H, Bizhani F, Bahari G, Taheri M. Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population. J Appl Oral Sci 2017; 25 (06) 650-656
• 19 Savitha S, Sharma SM, Veena S, Rekha R. Single nucleotide polymorphism of bone morphogenetic protein 4 gene: a risk factor of non-syndromic cleft lip with or without palate. Indian J Plast Surg 2015; 48 (02) 159-164