Polymorphisms of DNA repair genes XPD and XRCC1 and risk of cataract development Mustafa U ¨ nal a, * , Mehmet Gu ¨ven b , Bahadır Batar b , Ahmet O ¨ zaydın b , Ahmet Sarici c , Kazım Devrano˘ glu c a Department of Ophthalmology, Akdeniz University Medical Faculty, Antalya, Turkey b Department of Medical Biology, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey c Department of Ophthalmology, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey Received 21 October 2006; accepted in revised form 1 June 2007 Available online 14 June 2007 Abstract The association between oxidative or ultraviolet (UV) light induced DNA damage in the lens epithelium and the development of lens opacities, and the existence of DNA repair in lens epithelial cells have been reported. Polymorphisms of DNA repair enzymes may affect repair efficiency. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complemen- tation group D (XPD) codon 751 and X-ray cross-complementing group 1 (XRCC1) codon 399, in a sample of Turkish patients with maturity onset cataract. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we analysed XRCC1- Arg399Gln and XPD-Lys751Gln polymorphisms in 195 patients with cataract (75 patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30 with mixed type) and in 194 otherwise healthy control group of similar age. There was a significant difference between frequencies for XPD-751 Gln/Gln genotype in cataract patients (12%) and healthy controls (20%) (P ¼ 0.008, OR ¼ 0.40, 95% CI ¼ 0.20e 0.81). After stratification by the cataract subtypes, XPD-751 Gln/Gln genotype was found to be significantly different in patients with cortical (4%) type cataract in respect to control subjects (20%) (P ¼ 0.038, OR ¼ 0.16, 95% CI ¼ 0.04e0.64). In addition, the allele frequency of the C (Gln)-allele of XPD-Lys751Gln was found to be significantly different in mixed type cataract group (P ¼ 0.008, OR ¼ 0.48, 95% CI: 0.26e 0.90). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in XRCC1 gene between the groups. These findings suggest that polymorphism in XPD codon 751 may be associated with the development of maturity onset cataract. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: DNA repair genes; polymorphism; cataract 1. Introduction Age related cataract is the leading cause of blindness worldwide, with an estimated 18 million individuals bilater- ally blind (World Health Organization report). The etiology of age-related changes in the lens is not fully understood and is likely to be multifactorial. A growing body of research has focused on risk factors that might contribute to cataract de- velopment and preventive factors that might retard their growth (Asbell et al., 2005). Endogenous oxidative damage to proteins, lipids, and DNA has been hypothesized to be an important etiologic factor in aging and the development of systemic diseases such as can- cer, atherosclerosis, and ocular disorders including cataract, glaucoma, uveitis, and age-related macular degeneration (McCall and Frei, 1999; Ohia et al., 2005). Association be- tween oxidative stress and DNA damage has been well-known (Johnson and Barton, 2007). In recent years, many studies fo- cused on the association between DNA damage to the lens ep- ithelium and the development of lens opacities (Spector, 1995; * Corresponding author at: Department of Ophthalmology, Akdeniz Univer- sity Medical Faculty, Demircikara mah. 1426. sk. Zeybek apt. B blok. No: 14/ 12 Muratpas xa, Antalya, Turkey. Tel.: þ90 242 249 6000; fax: þ90 242 227 4490; mobile: þ90 533 621 6968. E-mail address: mustafaunalmd@gmail.com (M. U ¨ nal). 0014-4835/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2007.06.003 Experimental Eye Research 85 (2007) 328e334 www.elsevier.com/locate/yexer