Association between a Tetranucleotide Repeat Polymorphism of SPAG16 Gene and Cataract in Male Children

Purpose. Studies involving genotyping of STR markers at 2q34 have repeatedly found the region to host the disease haplotype for pediatric cataract. Present study investigated the association of D2S2944 marker, in sperm associated antigen 16 (SPAG16) gene and rs2289917 polymorphism, in γ-crystallin B gene, with childhood cataract. Methods. 97 pediatric cataract cases and 110 children with no ocular defects were examined for tetranucleotide repeat marker/SNP using PCR-SSLP/RFLP techniques. Polymorphisms were assessed for association using contingency tables and linkage disequilibrium among alleles of the markers was estimated. Energy-optimization program predicted the secondary structure models of repeats of D2S2944. Results. Seven alleles of D2S2944, with 9–15 “GATA” repeats, were observed. Frequency of the longer allele of D2S2944, ≥(GATA)(13) repeats, was 0.73 in cases and 0.56 in controls (P = 0.0123). Male children bearing ≥(GATA)(13) repeats showed >3-fold higher risk for cataract (CI(95%) = 1.43–7.00, P = 0.0043, P (c) = 0.0086) as compared to female children (OR = 1.19, CI(95%) = 0.49–2.92, P = 0.70). Cases with haplotype—≥(GATA)(13) of D2S2944 and “C” allele rs2289917—have a higher risk for pediatric cataract (OR = 2.952, CI(95%) = 1.595~5.463, P = 0.000453). >(GATA)(13 ) repeats formed energetically more favorable stem-loop structure. Conclusion. Intragenic microsatellite repeat expansion in SPAG16 gene increases predisposition to pediatric cataract by probably interfering posttranscriptional events and affecting the expression of adjacent lens transparency gene/s in a gender bias manner.