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Mitochondrial uncoupling protein 2 (UCP2) gene polymorphism − 866 G/A in the promoter region is associated with type 2 diabetes mellitus among Kashmiri population of Northern India

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Abstract

Objective

The study aimed to evaluate the association of UCP2 gene polymorphism − 866 G/A and its expression with diabetes predisposition in the North Indian population.

Methods

The study involved 850 subjects, including 425 each T2DM and control subjects. The serum metabolic and clinical parameters were estimated using standard protocols. The PCR–RFLP based genotyping was performed to determine UCP2 gene polymorphism, while the expression was measured by real-time quantitative PCR.

Results

The genotypic and allelic frequencies showed a significant difference in cases compared to controls (p < 0.05). The diabetes patients had a 4.2-fold decrease in UCP2 gene expression. The expression was 29.8 and 8.4 fold lower in diabetes patients with homozygous (AA) and heterozygous (GA) mutation at − 866 locus of UCP2 nucleotide sequence, respectively. When categorized according to age and BMI, the T2DM subjects with age ≥ 50 and BMI ≥ 25 had a 5.53 and 8.2-fold decrease in UCP2 expression, respectively. The diabetes subjects with homozygous and heterozygous mutation demonstrated a pathological increase in serum metabolic and clinical parameters, which corroborated with UCP2 gene expression, indicating a strong association between the two. Intriguingly, we did not find any association between − 866 G/A polymorphism of UCP2 with serum insulin levels.

Conclusion

Our investigation is the first among the studies conducted in Jammu and Kashmir to work on adipose tissue and UCP2 gene polymorphism. The association of − 866 G/A SNP of the UCP2 gene with its expression in diabetes patients appears to be an important genetic determinant in the progression of T2DM. Moreover, age ≥ 50 years and BMI ≥ 25 could be considered risk factors for developing T2DM in the studied population.

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Acknowledgements

We thank the Department of Science & Technology (DST), New Delhi, for financial assistance (File No. DST/INSPIRE/04/2017/001350) to Dr. Mohd Fareed. Special thanks to the study participants for their utmost support and cooperation. We also thank Dr. Sheikh Rayees Rafiq, a DBT Ramalingaswami Fellow, for helping us with his valuable advice with experiments.

Funding

The authors have no external support or funding to report.

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Authors and Affiliations

  1. Department of Biochemistry, Government Medical College, Srinagar, J&K, 190010, India

    Inshah Din, Sabhiya Majid, Jasiya Qadir & Hilal Wani

  2. Department of Clinical Biochemistry, University of Kashmir, Srinagar, J&K, 190010, India

    Inshah Din & Fouzia Rashid

  3. Department of Surgery, Government Medical College, Srinagar, J&K, 190010, India

    Mumtaz Din Wani

  4. Pharmacology Division, CSIR Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India

    Mohd Fareed

  5. Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India

    Mohd Fareed

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Contributions

ID and SM designed the study. ID, FR, MDW, JQ and HW contributed to the clinical and molecular experiments. ID, SM and MF analyzed and interpreted the data. ID, SM, FR, MDW, JQ, HW and MF were involved in drafting the manuscript. All authors critically reviewed and approved the manuscript.

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Correspondence to Sabhiya Majid or Mohd Fareed.

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The authors declare no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethics committee Govt. Medical College, Srinagar. All methods were performed following the guidelines and regulations of the Indian Council of Medical Research (ICMR), New Delhi.

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We obtained informed written consent from the participants involved in the study.

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Din, I., Majid, S., Rashid, F. et al. Mitochondrial uncoupling protein 2 (UCP2) gene polymorphism − 866 G/A in the promoter region is associated with type 2 diabetes mellitus among Kashmiri population of Northern India. Mol Biol Rep 50, 475–483 (2023). https://doi.org/10.1007/s11033-022-08055-z

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