PURPOSE: Recently, the neurotrophin-4 (NTF4), VAV2 and VAV3 genes have been implicated in primary open-angle glaucoma (POAG) in the European and Japanese populations, respectively. This study was conducted to determine their involvement in an Indian population with POAG and primary angle-closure glaucoma (PACG). METHODS: The entire NTF4 gene and the POAG-associated SNPs rs2156323 (VAV2) and rs2801219 (VAV3) and their flanking regions were screened by resequencing in a clinically well-characterized cohort of 537 subjects that included cases of POAG (n = 141), PACG (n = 111), and ethnically matched normal controls (n = 285). The data were analyzed by using appropriate statistical software. RESULTS: Resequencing of NTF4 revealed a nonsynonymous (A88V), silent (P151P) and two changes in the 3'UTR region, along with a known polymorphism (rs11669977) in cases of POAG; the PACG cases exhibited only the A88V variation. Of interest, the A88V mutation observed in Europeans was more prevalent in our normal control subjects (4.91%, 95% CI, 2.95-8.07) than in the POAG (2.14%, 95% CI, 0.73-6.11; P = 0.200) and PACG (2.85%, 95% CI, 0.97-8.06; P = 0.577) cases. There were no major differences in the presenting intraocular pressure, cup-to-disc ratio, and visual field defects among patients harboring the A88V variation. The other variations in NTF4 were not associated with the cases. The risk alleles of rs2156323 and rs2801219 in the Japanese were not associated with POAG (P = 0.533 and 0.133, respectively) and PACG (P = 0.223 and 0.394, respectively) in the Indian cohort. CONCLUSIONS: The present data indicate a lack of involvement of variations in NTF4, VAV2, and VAV3 with glaucoma pathogenesis in an Indian population.