Background: Orofacial clefts (OFC) are linked with several genetic and environmental factors. The aim of this study was to explore the association of potential risk factors with OFCs in India. Methods: This was a hospital-based, matched case-control (1:4 ratio; matching done for parity) study conducted in Hyderabad, Bengaluru, and Delhi-National Capital Region. Cases (nonsyndromic clefts) were recruited from treatment centers, while controls (live births) were recruited from maternity centers. p value 5 0.001), and delayed first conception (AOR, 2.55, 95% CI, 1.25-5.21, p 5 0.01) were found to be strongly associated with higher risk of OFCs. Supplementation with folic acid during first 3 months of pregnancy was not found to be protective against OFCs (AOR, 1.24; 95% CI, 0.59-2.58; p value 5 0.56). Conclusion: Our study confirmed the importance of family history as a risk factor for OFC. Our study did not show an association with folic acid supplementation but was underpowered to detect small effects. Our finding of higher risk among vegetarians requires replication.

AbstractCleft lip palate (CLP) is one of the common congenital anomalies with multifactorial etiology. Many genes are associated with its etiology. In one of the studies CRISPLD2 gene polymorphisms rs1546124, rs4783099, and rs16974880 were reported in the Chinese population. However, its role in the Indian population is not yet studied. Hence, this research was conducted on the Indian population to know the role of these high-risk polymorphisms in patients with nonsyndromic CLP. Following an inclusion and exclusion criteria, 20 multiplex CLP families were selected from a high volume cleft center in India. Genomic DNA was isolated from these families. Single nucleotide polymorphism (SNP) rs1546124, rs4783099, and rs16974880 were analyzed for their association using MassARRAY method. A whole-genome association analysis toolset, PLINK was used for statistical analysis. The polymorphisms followed Hardy–Weinberg equilibrium. None of the polymorphisms showed any significance. Hence the high-risk polymorphisms rs1546124, rs4783099, and rs16974880 are not associated with nonsyndromic CLP in Indian population.

Background. Cleft lip and palate (CLP) is a common congenital anomaly. Many genes, like MAPK4 andSOX-1OT, are associated with its etiology in different populations. High-risk markers on these genesreported in other populations were not studied in our population. Hence, the study aimed to determinethe association of MAPK4 and SOX-1OT polymorphisms in CLP in multiplex families. Methods. Based on inclusion and exclusion criteria, we selected 20 multiplex CLP families for thiscase‒control study, in which the affected individuals and healthy controls selected from these familieswere compared. Fifty subjects affected with cleft and 38 unaffected subjects were included in the study.The polymorphisms studied for the association consisted of rs726455 and rs2969972 in the genes SOX-1OT and MAPK4, respectively. DNA was isolated and sent for genotyping using the MassArray method.Plink, a whole-genome association analysis toolset, was used for statistical analysis. Results. Both polymorphisms followed Hardy–Weinberg equilibrium. The rs726455 of SOX-1OTyielded a P-value of 0.983 and an allelic odds ratio (OR) of 0.983. For rs2969972 of MAPK4, the P-valuewas 0.04 (significant), and the allelic OR was 0.51. Minor allele frequency (MAF) in the unaffectedsubjects was more than the MAF in the affected subjects for rs2969972. Conclusion. The results suggested that polymorphism rs726455 on SOX-1OT was not associated withfamilial cases of CLP. Since MAF in the unaffected subjects was more than the MAF-affected subjects,rs2969972 on MAPK4 is protective in the multiplex families.

BACKGROUND: Cleft lip palate is a common congenital anomaly with multifactorial etiology. Many high-risk markers at different loci were reported to be involved in its etiology. Advanced genetic research led to the discovery of evidence of a new linkage on 13q33.1-34 region at marker rs1830756 in two multigenerational Indian families. However, no further study was reported to confirm or validate this linkage in other families. Hence, the present study was designed.METHODS: Twenty multigenerational families affected by non-syndromic cleft lip palate were selected for the study. Polymorphisms, rs1830756, rs1323672, rs1935135 of FAM155A gene; rs1961495, rs953386, rs1411040 of COL4A1 gene; and rs726449, rs984300 of MYO16 gene were selected. Genomic DNA was isolated and sent for genetic analysis by single nucleotide polymorphism (SNP) genotyping using the MassArray method. Statistical analysis of the genomic data was done by PLINK. Bonferroni correction was applied and haplotype analysis was done using Haploview software.RESULTS: Polymorphisms followed the Hardy Weinberg Equilibrium. In the allelic association, all the polymorphisms analysed showed no statistical significance. Hence, there was no significant difference in the allelic frequencies between non-syndromic cleft lip palate patients and healthy controls. The odds ratio was not more than 1.6 for all the SNPs. Haplotype analysis showed that haplotypes were not significantly higher in non-syndromic cleft patients than in control subjects.CONCLUSION: There is no association between SNPs analysed in the locus 13q33.1-34 with cleft lip palate.KEYWORDS: cleft lip palate, chromosome, polymorphism