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XRCC1 and XPD DNA repair gene polymorphisms: a potential risk factor for glaucoma in the Pakistani population.

Yousaf S, Khan MI, Micheal S, Akhtar F, Ali SH, Riaz M, Ali M, Lall P, Waheed NK, den Hollander AI, Ahmed A, Qamar R - Mol. Vis. (2011)

Bottom Line: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005).The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

ABSTRACT

Purpose: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG).

Methods: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls.

Results: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ(2) = 12.1 [p < 0.005]), for both dominant (OR = 2.44 [95% CI = 1.33-4.47], p < 0.005) as well as recessive model (OR = 3.62 [95% CI = 1.45-9.01], p < 0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z = 3.00 [p < 0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.

Conclusions: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.

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Related in: MedlinePlus

Agarose gel electrophoresis of the polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis of XPD and XRCC1. (Lanes 1–5) PstI digested fragments of exon 23 c.2298A>C XPD SNP. (Lane 1) AA genotype consisting of two fragments; 290 and 146 bp. (Lanes 2, 3, and 5) AC genotype consisting of four fragments; 290, 227, 146 and 63 bp. (Lane 4) CC genotype consisting of three fragments; 227, 146, and 63 bp. (Lanes 6–9) MspI digested fragments of exon 10 c.1316G>A XRCC1 SNP. (Lane 7) GG genotype consisting of two fragments; 148 and 94 bp. (Lanes 6 and 8) AG genotype consisting of three fragments; 242, 148, and 94 bp. (Lane 9) AA genotype consisting of an undigested fragment of 242 bp.
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f1: Agarose gel electrophoresis of the polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis of XPD and XRCC1. (Lanes 1–5) PstI digested fragments of exon 23 c.2298A>C XPD SNP. (Lane 1) AA genotype consisting of two fragments; 290 and 146 bp. (Lanes 2, 3, and 5) AC genotype consisting of four fragments; 290, 227, 146 and 63 bp. (Lane 4) CC genotype consisting of three fragments; 227, 146, and 63 bp. (Lanes 6–9) MspI digested fragments of exon 10 c.1316G>A XRCC1 SNP. (Lane 7) GG genotype consisting of two fragments; 148 and 94 bp. (Lanes 6 and 8) AG genotype consisting of three fragments; 242, 148, and 94 bp. (Lane 9) AA genotype consisting of an undigested fragment of 242 bp.

Mentions: The PCR products were digested with MspI restriction enzyme (Fermentas, Burlington, Ontario) at 37 °C overnight, followed by electrophoretic separation on 2.5% agarose gels, along with a 100 bp DNA ladder (Invitrogen Inc., Carlsbad, CA). The “A” allele of the polymorphism rs25487 degenerates a MspI restriction site, resulting in two fragments of 148 and 94 bp for the GG genotype, three fragments of 242, 148, and 94 bp of the AG genotype, and a single fragment of 242 bp for the AA genotype (Figure 1).


XRCC1 and XPD DNA repair gene polymorphisms: a potential risk factor for glaucoma in the Pakistani population.

Yousaf S, Khan MI, Micheal S, Akhtar F, Ali SH, Riaz M, Ali M, Lall P, Waheed NK, den Hollander AI, Ahmed A, Qamar R - Mol. Vis. (2011)

Agarose gel electrophoresis of the polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis of XPD and XRCC1. (Lanes 1–5) PstI digested fragments of exon 23 c.2298A>C XPD SNP. (Lane 1) AA genotype consisting of two fragments; 290 and 146 bp. (Lanes 2, 3, and 5) AC genotype consisting of four fragments; 290, 227, 146 and 63 bp. (Lane 4) CC genotype consisting of three fragments; 227, 146, and 63 bp. (Lanes 6–9) MspI digested fragments of exon 10 c.1316G>A XRCC1 SNP. (Lane 7) GG genotype consisting of two fragments; 148 and 94 bp. (Lanes 6 and 8) AG genotype consisting of three fragments; 242, 148, and 94 bp. (Lane 9) AA genotype consisting of an undigested fragment of 242 bp.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102023&req=5

f1: Agarose gel electrophoresis of the polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis of XPD and XRCC1. (Lanes 1–5) PstI digested fragments of exon 23 c.2298A>C XPD SNP. (Lane 1) AA genotype consisting of two fragments; 290 and 146 bp. (Lanes 2, 3, and 5) AC genotype consisting of four fragments; 290, 227, 146 and 63 bp. (Lane 4) CC genotype consisting of three fragments; 227, 146, and 63 bp. (Lanes 6–9) MspI digested fragments of exon 10 c.1316G>A XRCC1 SNP. (Lane 7) GG genotype consisting of two fragments; 148 and 94 bp. (Lanes 6 and 8) AG genotype consisting of three fragments; 242, 148, and 94 bp. (Lane 9) AA genotype consisting of an undigested fragment of 242 bp.
Mentions: The PCR products were digested with MspI restriction enzyme (Fermentas, Burlington, Ontario) at 37 °C overnight, followed by electrophoretic separation on 2.5% agarose gels, along with a 100 bp DNA ladder (Invitrogen Inc., Carlsbad, CA). The “A” allele of the polymorphism rs25487 degenerates a MspI restriction site, resulting in two fragments of 148 and 94 bp for the GG genotype, three fragments of 242, 148, and 94 bp of the AG genotype, and a single fragment of 242 bp for the AA genotype (Figure 1).

Bottom Line: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005).The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

ABSTRACT

Purpose: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG).

Methods: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls.

Results: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ(2) = 12.1 [p < 0.005]), for both dominant (OR = 2.44 [95% CI = 1.33-4.47], p < 0.005) as well as recessive model (OR = 3.62 [95% CI = 1.45-9.01], p < 0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z = 3.00 [p < 0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.

Conclusions: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.

Show MeSH
Related in: MedlinePlus