Download PDF
CC BY 4.0 · Glob Med Genet 2022; 09(03): 208-211
DOI: 10.1055/s-0042-1748531
Original Article

Role of PAX7 Gene rs766325 and rs4920520 Polymorphisms in the Etiology of Non-syndromic Cleft Lip and Palate: A Genetic Study

Mahamad Irfanulla Khan 
1   Department of Orthodontics and Dentofacial Orthopedics, The Oxford Dental College, Bengaluru, India
,
Prashanth CS 
2   Department of Orthodontics and Dentofacial Orthopedics, DAPM R. V. Dental College, Bengaluru, India
,
Narasimhamurty Srinath 
3   Department of Oral and Maxillofacial Surgery, Krishnadevaraya College of Dental Sciences, Bengaluru, India
› Author Affiliations Funding None.
› Further Information
   Permissions and Reprints

Abstract

Non-syndromic cleft lip and palate (NSCLP) is one of the most common birth defects in humans with an overall prevalence of ∼1 in 700 live births around the world. The etiology of NSCLP is complex involving multiple genes, environmental factors, and gene-to-gene interactions. Several genome-wide associations (GWA) studies have shown the association of the paired box 7 (PAX7) gene in the etiology of cleft lip and palate in different populations worldwide. However, there are no reported studies on the association between the rs766325 and rs4920520 polymorphisms and the risk of developing NSCLP in the Indian population. Hence, the present study aimed to test for the probable association between rs766325 and rs4920520 polymorphisms among NSCLP Indian population using a case-parent trio design. Forty case-parent trios were selected from the cleft lip and palate center based on the inclusion and exclusion criteria. Genomic DNA was isolated from the cases and their parents. The rs766325 and rs4920520 polymorphisms of the PAX7 gene were analyzed for their association using the MassARRAY analysis. The statistical analysis was done using the PLINK software. The rs766325 and rs4920520 polymorphisms were tested for the Hardy–Weinberg equilibrium. None of the polymorphisms showed any statistical significance. Hence, the rs766325 and rs4920520 polymorphisms of the PAX7 gene were found to be not associated with NSCLP in the Indian case-parent trios.

Keywords

non-syndromic - cleft lip and palate - PAX7 - DNA extraction - genotyping


Publication History

Received: 30 December 2021

Accepted: 14 March 2022

Article published online:
15 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Huang Y, Wu J, Ma J. et al. Association between IRF6 SNPs and oral clefts in West China. J Dent Res 2009; 88 (08) 715-718
    CrossrefPubMedGoogle Scholar
  • 2 Kahraman A, Yüce S, Koçak ÖF, Canbaz Y, Işik D. Congenital lateral cleft palate of unknown etiology. J Craniofac Surg 2015; 26 (04) 1332-1333
    CrossrefPubMedGoogle Scholar
  • 3 Indencleef K, Hoskens H, Lee MK. et al. The intersection of the genetic architectures of orofacial clefts and normal facial variation. Front Genet 2021; 12: 626403
    CrossrefPubMedGoogle Scholar
  • 4 Huang L, Jia Z, Shi Y. et al. Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft. PLoS Genet 2019; 15 (10) e1008357
    CrossrefPubMedGoogle Scholar
  • 5 Khan AN, Prashanth CS, Srinath N. Genetic etiology of cleft lip and palate. AIMS Mol Sci 2020; 7: 328-348
    CrossrefGoogle Scholar
  • 6 Vanderas AP. Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review. Cleft Palate J 1987; 24 (03) 216-225
    PubMedGoogle Scholar
  • 7 Panamonta V, Pradubwong S, Panamonta M, Chowchuen B. Global birth prevalence of orofacial clefts: a systematic review. J Med Assoc Thai 2015; 98 (Suppl. 07) S11-S21
    PubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. Am J Med Genet C Semin Med Genet 2013; 163C (04) 246-258
    CrossrefPubMedGoogle Scholar
  • 10 Khan MI, Cs P, Srinath NM. Genetic factors in nonsyndromic orofacial clefts. Glob Med Genet 2020; 7 (04) 101-108
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Neela PK, Reddy SG, Husain A, Mohan V. Association of cleft lip and/or palate in people born to consanguineous parents: a 13year retrospective study from a very high volume cleft center. J Cleft Lip Palate Craniofacial Anomalies 2019; 6 (01) 33-37
    CrossrefGoogle Scholar
  • 12 Mansouri A, Stoykova A, Torres M, Gruss P. Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice. Development 1996; 122 (03) 831-838
    CrossrefPubMedGoogle Scholar
  • 13 Wilkie AO, Morriss-Kay GM. Genetics of craniofacial development and malformation. Nat Rev Genet 2001; 2 (06) 458-468
    CrossrefPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 Neela PK, Gosla SR, Husain A, Mohan V. CRISPLD2 gene polymorphisms with nonsyndromic cleft lip palate in Indian population. Glob Med Genet 2020; 7 (01) 22-25
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Neela PK, Gosla SR, Husain A, Mohan V, Thumoju S, Bv R. Association of MAPK4 and SOX1-OT gene polymorphisms with cleft lip palate in multiplex families: a genetic study. J Dent Res Dent Clin Dent Prospect 2020; 14 (02) 93-96
    CrossrefPubMedGoogle Scholar
  • 17 Neela PK, Reddy GS, Husain A, Mohan V, Thumoju S, Bv R. Association of single nucleotide polymorphisms on locus 18q21.1 in the etiology of nonsyndromic cleft lip palate (NSCLP) in Indian multiplex families. Glob Med Genet 2021; 8 (01) 24-31
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Khan MI, Cs P. Case-parent trio studies in cleft lip and palate. Glob Med Genet 2020; 7 (03) 75-79
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Zalc A, Rattenbach R, Auradé F, Cadot B, Relaix F. Pax3 and Pax7 play essential safeguard functions against environmental stress-induced birth defects. Dev Cell 2015; 33 (01) 56-66
    CrossrefPubMedGoogle Scholar
  • 20 Relaix F, Rocancourt D, Mansouri A, Buckingham M. A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature 2005; 435 (7044): 948-953
    CrossrefPubMedGoogle Scholar
  • 21 Beaty TH, Taub MA, Scott AF. et al. Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study. Hum Genet 2013; 132 (07) 771-781
    CrossrefPubMedGoogle Scholar
  • 22 Xiao Y, Taub MA, Ruczinski I. et al. Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios. Genet Epidemiol 2017; 41 (03) 244-250
    CrossrefPubMedGoogle Scholar
  • Beaty TH, Murray JC, Marazita ML. et al. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet 2010; 42 (06) 525-529
    CrossrefPubMedGoogle Scholar
  • 24 Sull JW, Liang KY, Hetmanski JB. et al. Maternal transmission effects of the PAX genes among cleft case-parent trios from four populations. Eur J Hum Genet 2009; 17 (06) 831-839
    CrossrefPubMedGoogle Scholar
  • 25 Guo Q, Li D, Meng X. et al. Association between PAX7 and NTN1 gene polymorphisms and nonsyndromic orofacial clefts in a northern Chinese population. Medicine (Baltimore) 2017; 96 (19) e6724
    CrossrefPubMedGoogle Scholar
  • 26 Duan SJ, Huang N, Zhang BH. et al. New insights from GWAS for the cleft palate among han Chinese population. Med Oral Patol Oral Cir Bucal 2017; 22 (02) e219-e227
    PubMedGoogle Scholar
  • 27 Butali A, Suzuki S, Cooper ME. et al. Replication of genome wide association identified candidate genes confirm the role of common and rare variants in PAX7 and VAX1 in the etiology of nonsyndromic CL(P). Am J Med Genet A 2013; 161A (05) 965-972
    CrossrefPubMedGoogle Scholar