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

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发表日期：

2024年7月18日

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Keerthi Kupsal,
Kishore Kumar Gundapaneni,
Chiranjeevi Padala,
Nivas Shyamala,
Ramanjaneyulu Kummari,
Saraswati Mudigonda,
Srilatha Gantala,
Venkata Balakrishna Sai Nyayapathi,
Krishnaveni Neelala,
Surekha Rani Hanumanth

摘要

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.