Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with nonsyndromic oral clefts

Abstract

Objective: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with substantial clinical and social impact, and whose causes include both genetic and environmental factors. Folate and homocysteine metabolism have been indicated to play a role in the etiology of NSCLP. The aim of this study was to determine the prevalence of NOS3 27-bp VNTR and to evaluate whether this polymorphism contributed to the risk of NSCLP. Material and methods: We studied the 27 base pair tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase (NOS3) gene in 230 unrelated individuals belong to 7 Indian populations along with 141 NSCLP cases and 142 unrelated controls. The genotyping was performed by polymerase chain reaction and electrophoresis. The data were statistically analysed using the χ2-test. Results: The NOS3 27-bp VNTR 4a allele is present in six of the seven populations analysed and allele frequencies range from 6.8% in Sugali to 23.5% in Madiga populations. NOS3 showed protective association with predisposition towards NSCLP for the heterozygous (4b/a) genotypes (4b/b vs. 4b/a: OR =0.58, 95% CI =0.34 to 0.99, p=0.044). Conclusions: The current study suggests significant differences in the frequency of the NOS3 VNTR allele across the populations. There is protective association between NOS3 27-bp VNTR polymorphism and NSCLP in the Indian population.