{"title":"FAS -670 G > A 和 FASLG -844 T > C 多态性及其循环血清可溶性标记物与 2 型糖尿病风险的关系：一项病例对照研究","authors":"Keerthi Kupsal, Kishore Kumar Gundapaneni, Chiranjeevi Padala, Nivas Shyamala, Ramanjaneyulu Kummari, Saraswati Mudigonda, Srilatha Gantala, Venkata Balakrishna Sai Nyayapathi, Krishnaveni Neelala, Surekha Rani Hanumanth","doi":"10.1007/s13410-024-01371-z","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Type 2 Diabetes (T2D) is catalyzed by enhanced oxidative stress which induces pancreatic beta cell apoptosis. Genetic variations in extrinsic death pathway genes like <i>FAS</i> and <i>FASLG</i> might alter the apoptotic activity and cause individuals susceptible to T2D. </p><h3 data-test=\"abstract-sub-heading\">Objective </h3><p>The present study aimed to evaluate the oxidative stress markers, the association of <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms and their serum soluble levels in type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Serum nitrates/nitrites and oxidative DNA damage levels were estimated by Griess reagent assay and Comet assay, respectively. Genotyping of <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms were determined by PCR–RFLP method. Serum soluble FAS and soluble FASLG levels were estimated by ELISA. Statistical analyses were performed using Open-epi, SNPStats and SPSS software. Gene–gene and gene-epidemiological interactions were performed using MDR software.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Nitrates/nitrites and oxidative DNA damage levels were significantly higher in T2D patients compared to controls. Molecular analysis has revealed the association of <i>FAS</i> -670 GG and <i>FASLG</i> -844 CC genotypes with increased risk of T2D. In addition, it was found that T2D patients had significantly lower serum soluble FAS levels and higher serum soluble FASLG levels. Further, MDR gene–gene interaction analysis has demonstrated strong interaction between the genes, whereas gene-epidemiological interactions have shown additive effects on the disease phenotype.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The higher levels of nitrates/nitrites and oxidative DNA damage in individuals with T2D highlight the role of oxidative stress in T2D development. Additionally, the association between the <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms and elevated risk of T2D underscores the plausible impact of genetic variants on T2D susceptibility.</p>","PeriodicalId":50328,"journal":{"name":"International Journal of Diabetes in Developing Countries","volume":"34 1","pages":""},"PeriodicalIF":0.7000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association of FAS -670 G > A and FASLG -844 T > C polymorphisms and their circulating serum soluble markers with risk of type 2 diabetes: a case control study\",\"authors\":\"Keerthi Kupsal, Kishore Kumar Gundapaneni, Chiranjeevi Padala, Nivas Shyamala, Ramanjaneyulu Kummari, Saraswati Mudigonda, Srilatha Gantala, Venkata Balakrishna Sai Nyayapathi, Krishnaveni Neelala, Surekha Rani Hanumanth\",\"doi\":\"10.1007/s13410-024-01371-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Type 2 Diabetes (T2D) is catalyzed by enhanced oxidative stress which induces pancreatic beta cell apoptosis. Genetic variations in extrinsic death pathway genes like <i>FAS</i> and <i>FASLG</i> might alter the apoptotic activity and cause individuals susceptible to T2D. </p><h3 data-test=\\\"abstract-sub-heading\\\">Objective </h3><p>The present study aimed to evaluate the oxidative stress markers, the association of <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms and their serum soluble levels in type 2 diabetes.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Serum nitrates/nitrites and oxidative DNA damage levels were estimated by Griess reagent assay and Comet assay, respectively. Genotyping of <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms were determined by PCR–RFLP method. Serum soluble FAS and soluble FASLG levels were estimated by ELISA. Statistical analyses were performed using Open-epi, SNPStats and SPSS software. Gene–gene and gene-epidemiological interactions were performed using MDR software.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Nitrates/nitrites and oxidative DNA damage levels were significantly higher in T2D patients compared to controls. Molecular analysis has revealed the association of <i>FAS</i> -670 GG and <i>FASLG</i> -844 CC genotypes with increased risk of T2D. In addition, it was found that T2D patients had significantly lower serum soluble FAS levels and higher serum soluble FASLG levels. Further, MDR gene–gene interaction analysis has demonstrated strong interaction between the genes, whereas gene-epidemiological interactions have shown additive effects on the disease phenotype.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>The higher levels of nitrates/nitrites and oxidative DNA damage in individuals with T2D highlight the role of oxidative stress in T2D development. Additionally, the association between the <i>FAS</i> -670 G > A and <i>FASLG</i> -844 T > C polymorphisms and elevated risk of T2D underscores the plausible impact of genetic variants on T2D susceptibility.</p>\",\"PeriodicalId\":50328,\"journal\":{\"name\":\"International Journal of Diabetes in Developing Countries\",\"volume\":\"34 1\",\"pages\":\"\"},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2024-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Diabetes in Developing Countries\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13410-024-01371-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Diabetes in Developing Countries","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13410-024-01371-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
背景2型糖尿病（T2D）是由氧化应激增强诱导胰腺β细胞凋亡催化的。FAS和FASLG等外源性死亡通路基因的遗传变异可能会改变凋亡活性，并导致个体易患T2D。本研究旨在评估 2 型糖尿病患者的氧化应激标记物、FAS -670 G > A 和 FASLG -844 T > C 多态性及其血清可溶性水平的相关性。采用 PCR-RFLP 法测定 FAS -670 G > A 和 FASLG -844 T > C 多态性的基因分型。血清可溶性 FAS 和可溶性 FASLG 水平通过 ELISA 法进行评估。使用 Open-epi、SNPStats 和 SPSS 软件进行统计分析。结果与对照组相比，T2D 患者的硝酸盐/亚硝酸盐和氧化 DNA 损伤水平明显升高。分子分析表明，FAS -670 GG 和 FASLG -844 CC 基因型与 T2D 风险增加有关。此外，研究还发现，T2D 患者的血清可溶性 FAS 水平明显较低，而血清可溶性 FASLG 水平较高。此外，MDR 基因与基因之间的相互作用分析表明，基因之间存在很强的相互作用，而基因与流行病学之间的相互作用则显示出对疾病表型的叠加效应。此外，FAS -670 G > A 和 FASLG -844 T > C 多态性与 T2D 风险升高之间的关联强调了基因变异对 T2D 易感性的合理影响。
Association of FAS -670 G > A and FASLG -844 T > C polymorphisms and their circulating serum soluble markers with risk of type 2 diabetes: a case control study
Background
Type 2 Diabetes (T2D) is catalyzed by enhanced oxidative stress which induces pancreatic beta cell apoptosis. Genetic variations in extrinsic death pathway genes like FAS and FASLG might alter the apoptotic activity and cause individuals susceptible to T2D.
Objective
The present study aimed to evaluate the oxidative stress markers, the association of FAS -670 G > A and FASLG -844 T > C polymorphisms and their serum soluble levels in type 2 diabetes.
Methods
Serum nitrates/nitrites and oxidative DNA damage levels were estimated by Griess reagent assay and Comet assay, respectively. Genotyping of FAS -670 G > A and FASLG -844 T > C polymorphisms were determined by PCR–RFLP method. Serum soluble FAS and soluble FASLG levels were estimated by ELISA. Statistical analyses were performed using Open-epi, SNPStats and SPSS software. Gene–gene and gene-epidemiological interactions were performed using MDR software.
Results
Nitrates/nitrites and oxidative DNA damage levels were significantly higher in T2D patients compared to controls. Molecular analysis has revealed the association of FAS -670 GG and FASLG -844 CC genotypes with increased risk of T2D. In addition, it was found that T2D patients had significantly lower serum soluble FAS levels and higher serum soluble FASLG levels. Further, MDR gene–gene interaction analysis has demonstrated strong interaction between the genes, whereas gene-epidemiological interactions have shown additive effects on the disease phenotype.
Conclusion
The higher levels of nitrates/nitrites and oxidative DNA damage in individuals with T2D highlight the role of oxidative stress in T2D development. Additionally, the association between the FAS -670 G > A and FASLG -844 T > C polymorphisms and elevated risk of T2D underscores the plausible impact of genetic variants on T2D susceptibility.
期刊介绍：
International Journal of Diabetes in Developing Countries is the official journal of Research Society for the Study of Diabetes in India. This is a peer reviewed journal and targets a readership consisting of clinicians, research workers, paramedical personnel, nutritionists and health care personnel working in the field of diabetes. Original research articles focusing on clinical and patient care issues including newer therapies and technologies as well as basic science issues in this field are considered for publication in the journal. Systematic reviews of interest to the above group of readers are also accepted.
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