Association of single nucleotide polymorphisms in WNT genes with the risk of nonsyndromic cleft lip with or without cleft palate

Abstract

Nonsyndromic cleft lip with or without cleft palate is a common congenital deformity worldwide with multifaceted etiology. Interaction of genes and environmental factors has been indicated to be related with susceptibility to nonsyndromic cleft lip with or without cleft palate. Some WNT genes which are involved in craniofacial embryogenesis may play a key role in the pathogenesis of nonsyndromic cleft lip with or without cleft palate. In the present study, we aimed to inspect the relationship between WNT3 (rs3809857 and rs9890413), WNT3A (rs752107 and rs3121310), and WNT10a rs201002930 (c.392 C>T) polymorphisms and nonsyndromic cleft lip with or without cleft palate in an Iranian population. The present case-control study was carried out on 120 unrelated nonsyndromic cleft lip with or without cleft palate patients and 112 healthy subjects. The variants were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. The findings suggest that the rs3809857 polymorphism significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.16, 95% confidence interval = 0.03-0.75, P = 0.020, TT vs GG), recessive (odds ratio = 0.16, 95% confidence interval = 0.03-0.72, P = 0.009, TT vs GG + GT) inheritance models. The rs9890413 variant marginally decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.41, 95% confidence interval = 0.17-0.99, P = 0.047, AG vs AA) model. Regarding C392T variant, the findings revealed that this variant significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.24, 95% confidence interval = 0.10-0.58, P = 0.002, CT vs CC) and allele (odds ratio = 0.26, 95% confidence interval = 0.11-0.62, P = 0.002, T vs C) models. No significant association was observed between the rs752107 and rs3121310 variants and risk/protection of nonsyndromic cleft lip with or without cleft palate. Stratified analysis showed that WNT10a rs201002930 (c.392 C>T) significantly decreased the risk of cleft lip with cleft palate and cleft palate only. In summary, the results suggest an association between WNT genes polymorphisms and the risk nonsyndromic cleft lip with or without cleft palate in a sample of the southeast Iranian population.

Association of the WNT3 polymorphisms and non-syndromic cleft lip with or without cleft palate: evidence from a meta-analysis

“…The remaining eight articles went into full-text assessment for eligibility, and one was removed because of unavailable data [ 17 ]. Seven studies [ 18–24 ] were incorporated into the qualitative synthesis, and five [ 19 , 21–24 ] were included in the final meta-analysis. The process of literature selection process is presented in Figure 1 .…”

“…All the studies were case–control studies in design. Of them, two were carried out in China [ 18 , 23 ], two in Iran [ 19 , 24 ], one in U.S.A. [ 22 ], one in Poland [ 21 ], and another one in Estonia [ 20 ]. The sample size of individual study ranged from 104 to 463 for cases, and 112 to 606 for controls.…”

“…Meta-analysis for rs3809857 polymorphism and NSCL/P susceptibility was available on four studies including 679 cases and 976 controls [ 19 , 21 , 23 , 24 ]. As no heterogeneity amongst the four studies was observed ( P =0.98, I 2 = 0%), the fixed-effect model was employed for calculating the association between rs3809857 and NSCL/P.…”

“…Meta-analysis for rs9890413 polymorphism and NSCL/P susceptibility was based on five studies [ 19 , 21–24 ], containing 1142 cases and 1279 controls. Because considerable heterogeneity amongst the five studies was detected ( P =0.0004, I 2 = 81%), the random-effect model was applied for data combination.…”

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population, a preliminary report

“…Although, the exact cause of NSCL/P is remained unknown, it is proposed that the interaction of genetic and environmental factors play a significant role in the pathogenesis of the disease (Dixon et al., ). A number of genetic polymorphisms were found to be associated with the risk of NSCL/P in the Iranian population (Rafighdoost et al., , , ; Rafighdoost, Hashemi, Asadi, & Bahari, ; Rafiqdoost et al., ).…”