Mehra Shipra, Kapur Suman, Ganesh Suma
School of Public Health and Psychiatry Institute, University of Illinois, 1601 West Taylor Street, 306N Chicago, IL 60612, USA.
Biological Sciences Department, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R. R. District, Hyderabad 500078, India.
J Biomark. 2013;2013:810395. doi: 10.1155/2013/810395. Epub 2013 Sep 27.
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 (CI95% = 1.43-7.00, P = 0.0043, P c = 0.0086) as compared to female children (OR = 1.19, CI95% = 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, CI95% = 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.
目的。涉及对2q34处STR标记进行基因分型的研究反复发现该区域存在小儿白内障的疾病单倍型。本研究调查了精子相关抗原16（SPAG16）基因中的D2S2944标记以及γ-晶体蛋白B基因中的rs2289917多态性与儿童白内障的关联。方法。采用PCR-SSLP/RFLP技术对97例小儿白内障病例和110例无眼部缺陷的儿童进行四核苷酸重复标记/SNP检测。使用列联表评估多态性的关联性，并估计标记等位基因之间的连锁不平衡。能量优化程序预测了D2S2944重复序列的二级结构模型。结果。观察到D2S2944的7个等位基因，具有9 - 15个“GATA”重复序列。D2S2944较长等位基因（≥(GATA)13重复序列）的频率在病例组中为0.73，在对照组中为0.56（P = 0.0123）。携带≥(GATA)13重复序列的男性儿童患白内障的风险比女性儿童高3倍以上（CI95% = 1.43 - 7.00，P = 0.0043，Pc = 0.0086）（女性儿童的OR = 1.19，CI95% = 0.49 - 2.92，P = 0.70）。具有D2S2944单倍型≥(GATA)且rs2289917为“C”等位基因的病例患小儿白内障的风险更高（OR = 2.952，CI95% = 1.595 - 5.463，P = 0.000453）。≥(GATA)13重复序列形成了能量上更有利的茎环结构。结论。SPAG16基因内的微卫星重复序列扩增可能通过干扰转录后事件并以性别偏倚的方式影响相邻晶状体透明基因的表达，增加了小儿白内障的易感性。
