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An Analysis of the Associations of Polymorphic Variants of the LEPR (rs1137100), LRP5 (rs3736228), and LPL (rs320) Genes with the Risk of Developing Type 2 Diabetes Mellitus

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Abstract

Diabetes mellitus is a hereditary predisposed multifactorial disease. However, the genetic mechanisms of its development have not been fully revealed yet. We conducted a search for associations of polymorphic variants of the LEPR (rs1137100), LRP5 (rs3736228), and LPL (rs320) genes involved in the development of obesity with the development of type 2 diabetes mellitus. The association with development of the disease was established for the T allele of the LRP5 locus (rs3736228) (p = 0.029, OR = 1.46). The rs1137100 locus (p = 0.032) of the LEPR gene was shown to be associated with the body mass index (BMI), but it was not connected with the presence of type 2 diabetes mellitus. Risk markers of development of type 2 diabetes included the T allele of the rs3736228 locus of the LRP5 gene (OR = 1.74, p = 0.012) and the G allele of the rs320 locus of the LPL gene (OR = 1.39, p = 0.027). Statistically significant association was only found in the group of nonobese patients. A decrease in the level of low-density lipoprotein was observed in individuals with the TT genotype of the LPL locus (rs320) (p = 0.04). Individuals with the GT and GG genotypes of this locus had a lower cholesterol level (p = 0.027). A decrease in the level of BMI (p = 0.012) and a decrease in the concentration of triglycerides in the blood (p = 0.00000004) were detected in carriers of the CC genotype of the LRP5 rs3736228 locus.

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ACKNOWLEDGMENTS

This study was supported in part by the Russian Foundation for Basic Research, project no. 18-015-00050 and the Ministry of Science and Higher Education of the Russian Federation № АААА-А16-116020350032-1. Biological material (DNA) for the study was taken from the collection “Collection of Human Biological Materials IBG USC RAS” IBG USC RAS, supported by the program of bio-resource collections FANO Russia (agreement no. 007-030164/2).

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, 450054, Ufa, Russia

    O. V. Kochetova, G. F. Korytina, L. Z. Akhmadishina & O. E. Mustafina

  2. Bashkortostan State Medical University, 450000, Ufa, Russia

    D. S. Avzaletdinova, L. F. Sharipova & T. V. Morugova

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  1. O. V. Kochetova
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  2. D. S. Avzaletdinova
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Correspondence to O. V. Kochetova.

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Statement of compliance with standards of research involving humans as subjects. The study was approved by the Ethics Committee of the Institute of Biochemistry and Genetics. All participants in the study gave their informed voluntary consent to the use of the biological material.

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Translated by I. Shipounova

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Kochetova, O.V., Avzaletdinova, D.S., Sharipova, L.F. et al. An Analysis of the Associations of Polymorphic Variants of the LEPR (rs1137100), LRP5 (rs3736228), and LPL (rs320) Genes with the Risk of Developing Type 2 Diabetes Mellitus. Russ J Genet 55, 495–503 (2019). https://doi.org/10.1134/S1022795419040057

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