Publication: DNA onarım enzim polimorfizmi ve tip 2 diyabetle ilişkisi
Abstract
Amaç: Yapılan çalışmalar hiperglisemi ve diyabetik komplikasyonlar ile oksidatif stres, DNA hasarı ve onarımı arasında güçlü bir ilişki olduğunu işaret etmektedir. Bu tez çalışmasının amacı; Türk popülasyonunda XRCC3 geni T241M (rs86153) ve XRCC1 geni A339G (rs25487) polimorfizminin tip 2 diyabete (T2DM) ve diyabetik nefropatiye (DN) yatkınlıkta rolünün araştırılmasıdır. Gereç ve yöntem: XRCC3 geni T241M ve XRCC1 geni A339G polimorfizminin genotip ve allel frekanslarının dağılımı polimeraz zincir reaksiyonu-restriksiyon fragment uzunluğu (PCR-RFLP) ile belirlenmiştir. Çalışma populasyonu; T2DM grubu 116; DN grubu 50 hasta ve normal glukoz metabolizmasına sahip 72 sağlıklı birey olmak üzere 238 gönüllüden oluşmaktadır. Bulgular: Çoklu değişken analizi sonuçlarına göre; XRCC1 geninin 399 Gln alleli ile T2DM ve DN arasında istatistiksel anlamlı bir ilişki gözlenmiştir (sırasıyla p<0,05, OR=3,09 %95 CI=1,14-8,40 ve p<0,05, OR= 3,29, %95 CI=1,23-8,80). XRCC3 geni T241M polimorfizminin T2DM ve DN üzerinde istatistiksel anlamlı bir etkisi bulunmamıştır. Ayrıca, çoklu değişken analizine göre erkek cinsiyeti (p<0,5), 45 yaşın üstünde olmanın (p<0,001) 25’den büyük BMI’nın (p<0,001) ve aile diyabet öyküsünün (p<0,001) T2DM riskindeki rolü ve erkek olmanın (p<0,001) ve 65 yaşın üstünde olmanın (p<0,05) DN riskindeki rolü anlamlı bulunmuştur. XRCC1 geni A399G ile XRCC3 geni T241M polimorfizmi arasında etkileşme değerlendirildiğinde; XRCC1 Gln alleli ile XRCC3 Met allelinin birlikte T2DM riskini istatistiksel olarak anlamlı düzeyde arttırdığı gözlenmiştir (p<0,001, OR=4,11, %95 CI= 1,84-9,23). Sonuçlar: Çalışmanın sonuçlarına göre XRCC3 geni T241M polimorfizminin T2DM ve DN’ye yatkınlıkta ilişkisi bulunmamıştır ve benzer çalışmaların farklı etnik populasyonlarda, daha büyük örneklem büyüklüklerinde yapılması; diyabete yatkınlıkta XRCC1 geni A399G polimorfizminin etkisini belirlemede katkı sağlayacaktır. Anahtar sözcükler: Tip 2 Diyabet, DNA onarım gen polimorfizmi, XRCC1, XRCC3
Aim: Increasing number of experimental and clinical studies suggest that there is a close link between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy. The aim of this study was to explore whether the T241M polymorphic variant of XRRC3 gene and A399G polymorphic variant of XRCC1 gene is associated with an increased susceptibility to type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Turkish population. Material-Method: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used to determine the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (rs861539) and. A399G polymorphism of XRCC1 gene (rs25487). The study population included 238 subjects; 116 had type 2 diabetes mellitus, 50 had diabetic nephropathy and 72 had normal glucose metabolism. Results: Our results showed that there is a significant association between 399Gln allele of XRCC1 gene and T2DM or DN according to the multiple logistic regression analysis (p<0,05, OR=3,09 %95 CI=1,14-8,40 and p<0,05, OR= 3,29, %95 CI=1,23-8,80 respectively). There is no statistically significant association between T241M polymorphism of XRRC3 gene and T2DM or DN. The multiple logistic regression revealed that being male (p<0,05), older than 45 years of age <0,001), BMI≥25(p<0,001), family history(p<0,001) had a significant impact on T2DM patients and also being male (p<0,001) older than 65 years of age (p<0,05) had a significant effect on DN development. Also, combined analysis of two genes suggested that 399Gln allele of XRCC1 gene combined with 241Met allele of XRCC3 gene had a synergistic effect on increasing the risk of T2DM (p<0,001, OR=4,11, %95 CI= 1,84-9,23). Conclusion: The results of this study suggests that T241M polymorphic variant of XRRC3 gene is not associated with an increased susceptibility to T2DM and DN in the studied population. There is a need to clarify the potential impact of 399Gln allele of XRCC1 on predisposition to T2DM and DN with larger sample size and different ethnicities. Key words: Type 2 Diabetes Mellitus, DNA repair gene, XRCC1, XRCC3
Aim: Increasing number of experimental and clinical studies suggest that there is a close link between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy. The aim of this study was to explore whether the T241M polymorphic variant of XRRC3 gene and A399G polymorphic variant of XRCC1 gene is associated with an increased susceptibility to type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Turkish population. Material-Method: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used to determine the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (rs861539) and. A399G polymorphism of XRCC1 gene (rs25487). The study population included 238 subjects; 116 had type 2 diabetes mellitus, 50 had diabetic nephropathy and 72 had normal glucose metabolism. Results: Our results showed that there is a significant association between 399Gln allele of XRCC1 gene and T2DM or DN according to the multiple logistic regression analysis (p<0,05, OR=3,09 %95 CI=1,14-8,40 and p<0,05, OR= 3,29, %95 CI=1,23-8,80 respectively). There is no statistically significant association between T241M polymorphism of XRRC3 gene and T2DM or DN. The multiple logistic regression revealed that being male (p<0,05), older than 45 years of age <0,001), BMI≥25(p<0,001), family history(p<0,001) had a significant impact on T2DM patients and also being male (p<0,001) older than 65 years of age (p<0,05) had a significant effect on DN development. Also, combined analysis of two genes suggested that 399Gln allele of XRCC1 gene combined with 241Met allele of XRCC3 gene had a synergistic effect on increasing the risk of T2DM (p<0,001, OR=4,11, %95 CI= 1,84-9,23). Conclusion: The results of this study suggests that T241M polymorphic variant of XRRC3 gene is not associated with an increased susceptibility to T2DM and DN in the studied population. There is a need to clarify the potential impact of 399Gln allele of XRCC1 on predisposition to T2DM and DN with larger sample size and different ethnicities. Key words: Type 2 Diabetes Mellitus, DNA repair gene, XRCC1, XRCC3