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Polymorphisms in two DNA repair genes (XPD and XRCC1)--association with age related cataracts.

Padma G, Mamata M, Reddy KR, Padma T - Mol. Vis. (2011)

Bottom Line: The association between DNA damage to the lens epithelium and the development of lens opacities has been reported in many studies.Considering the types of cataract, XPD-312 Asn/Asn genotype was found to be significantly different in patients with cortical (29%) type in comparison to controls (13.2%; p=0.03, OR=2.39, 95% CI=1.11-5.12).No statistically significant difference was found for the genotypic and allelic distributions of the polymorphism in XRCC1.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Osmania University, Tarnaka, Hyderabad, A.P, India. padmatirunilai@gmail.com

ABSTRACT

Purpose: Age related cataract is the leading cause of blindness in the world today. The association between DNA damage to the lens epithelium and the development of lens opacities has been reported in many studies. Polymorphisms of DNA repair enzymes may affect repair efficiency and thereby lead to the development of age related cataract.

Methods: In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group (XPD) codon 312 and X-ray complementing group1 (XRCC1) codon 399, in a sample of 208 cataract patients (69 with cortical, 69 with nuclear and 70 with posterior sub capsular) and 151 sex and age matched healthy controls. XPD genotype was determined by Amplification Refractory Mutation System (ARMS) while XRCC1 was genotyped using the PCR-RFLP method.

Results: There was a significant difference between frequencies for XPD-312 Asn/Asn genotype in cataract patients (21.6%) and healthy controls (13.2%; p=0.03, OR=1.97, 95% CI=1.06-3.63). Considering the types of cataract, XPD-312 Asn/Asn genotype was found to be significantly different in patients with cortical (29%) type in comparison to controls (13.2%; p=0.03, OR=2.39, 95% CI=1.11-5.12). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphism in XRCC1. The MDR interaction analysis revealed weak synergism between the markers XPD-Asp312Asn and XRCC1-Arg399Gln contributing to cataract. It also showed that the AA genotype of XPD-Asp312Asn polymorphism when present in combination with the GA genotype of XRCC1-Arg399Gln had a fivefold and with AA had a fourfold risk for developing cataract.

Conclusions: The present study suggests that a polymorphism in XPD codon 312 may be associated with the development of maturity onset cataract. This is the first report on the association of XPD Asp312Asn polymorphism with maturity onset cataract.

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Related in: MedlinePlus

Distribution of high-risk (dark shaded) and low-risk (light shaded) genotypic combinations of the markers studied. The summary of the distribution illustrates the no. of patients (left bars) and controls (right bars) for each genotype combinations.
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f1: Distribution of high-risk (dark shaded) and low-risk (light shaded) genotypic combinations of the markers studied. The summary of the distribution illustrates the no. of patients (left bars) and controls (right bars) for each genotype combinations.

Mentions: The present data included polymorphisms Asp312Asn Arg399Gln as the over all best model with maximum testing accuracy of 0.5100 and CV consistency of 10/10. But the combination was not found to be significantly contributing to cataract. High-risk (dark gray) and low-risk (light gray) genotypic combinations were determined based on the threshold value for the present data which was 1.37 (208/151; Figure 1). It was observed that AA genotype of XPD Asp312Asn when present in combination with GA genotype of XRCC1 showed a fivefold risk (23/4) while when present with AA a fourfold risk (4/1) for developing cataract.


Polymorphisms in two DNA repair genes (XPD and XRCC1)--association with age related cataracts.

Padma G, Mamata M, Reddy KR, Padma T - Mol. Vis. (2011)

Distribution of high-risk (dark shaded) and low-risk (light shaded) genotypic combinations of the markers studied. The summary of the distribution illustrates the no. of patients (left bars) and controls (right bars) for each genotype combinations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3021570&req=5

f1: Distribution of high-risk (dark shaded) and low-risk (light shaded) genotypic combinations of the markers studied. The summary of the distribution illustrates the no. of patients (left bars) and controls (right bars) for each genotype combinations.
Mentions: The present data included polymorphisms Asp312Asn Arg399Gln as the over all best model with maximum testing accuracy of 0.5100 and CV consistency of 10/10. But the combination was not found to be significantly contributing to cataract. High-risk (dark gray) and low-risk (light gray) genotypic combinations were determined based on the threshold value for the present data which was 1.37 (208/151; Figure 1). It was observed that AA genotype of XPD Asp312Asn when present in combination with GA genotype of XRCC1 showed a fivefold risk (23/4) while when present with AA a fourfold risk (4/1) for developing cataract.

Bottom Line: The association between DNA damage to the lens epithelium and the development of lens opacities has been reported in many studies.Considering the types of cataract, XPD-312 Asn/Asn genotype was found to be significantly different in patients with cortical (29%) type in comparison to controls (13.2%; p=0.03, OR=2.39, 95% CI=1.11-5.12).No statistically significant difference was found for the genotypic and allelic distributions of the polymorphism in XRCC1.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Osmania University, Tarnaka, Hyderabad, A.P, India. padmatirunilai@gmail.com

ABSTRACT

Purpose: Age related cataract is the leading cause of blindness in the world today. The association between DNA damage to the lens epithelium and the development of lens opacities has been reported in many studies. Polymorphisms of DNA repair enzymes may affect repair efficiency and thereby lead to the development of age related cataract.

Methods: In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group (XPD) codon 312 and X-ray complementing group1 (XRCC1) codon 399, in a sample of 208 cataract patients (69 with cortical, 69 with nuclear and 70 with posterior sub capsular) and 151 sex and age matched healthy controls. XPD genotype was determined by Amplification Refractory Mutation System (ARMS) while XRCC1 was genotyped using the PCR-RFLP method.

Results: There was a significant difference between frequencies for XPD-312 Asn/Asn genotype in cataract patients (21.6%) and healthy controls (13.2%; p=0.03, OR=1.97, 95% CI=1.06-3.63). Considering the types of cataract, XPD-312 Asn/Asn genotype was found to be significantly different in patients with cortical (29%) type in comparison to controls (13.2%; p=0.03, OR=2.39, 95% CI=1.11-5.12). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphism in XRCC1. The MDR interaction analysis revealed weak synergism between the markers XPD-Asp312Asn and XRCC1-Arg399Gln contributing to cataract. It also showed that the AA genotype of XPD-Asp312Asn polymorphism when present in combination with the GA genotype of XRCC1-Arg399Gln had a fivefold and with AA had a fourfold risk for developing cataract.

Conclusions: The present study suggests that a polymorphism in XPD codon 312 may be associated with the development of maturity onset cataract. This is the first report on the association of XPD Asp312Asn polymorphism with maturity onset cataract.

Show MeSH
Related in: MedlinePlus