Polymorphism of the rs1421085 locus of the FTO gene in human populations: genogeographic aspect

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Abstract

The variability of the FTO gene is of great interest to geneticists and clinicians because of the association of polymorphic variants of this gene in human populations with body weight and obesity, which in turn leads to a variety of diseases. One of the most studied polymorphic loci of the FTO gene is rs1421085. The T®C substitution in this locus results in the rs1421085-C allele, which increases the risk of obesity-related pathologies. The study of human brown adipose tissue has revealed that individuals carrying the rs1421085-C allele exhibit a heightened expression of thermogenic genes and thermogenesis in general compared to T carriers. This observation led to the formulation of the hypothesis that the distinctive patterns of the rs1421085-C geographical distribution in populations reflect the processes of human adaptation to cold, particularly in the northern regions of the planet. To test this hypothesis, we conducted a study on the distribution of polymorphic variants of the rs1421085 locus in modern and ancient populations of Siberia and other regions of the world. The results demonstrated that the frequency of the rs1421085-C variant did not exhibit an increase in the northern direction in both modern and ancient Siberian populations and is maximal in populations of the Middle East and Europe. It seems plausible that this variant of the FTO gene polymorphism may have been a target for natural selection at the earliest stages of adaptation of ancient humans to cold, in the territory of Western Eurasia.

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B. А. Malyarchuk

Institute of Biological Problems of the North, Far East Branch of the Russian Academy of Sciences

Author for correspondence.
Email: malbor@mail.ru
Russian Federation, Magadan

A. N. Litvinov

Institute of Biological Problems of the North, Far East Branch of the Russian Academy of Sciences

Email: malbor@mail.ru
Russian Federation, Magadan

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2. Figure. Distribution of the rs1421085-C variant in the world population. The black dots on the map mark the reference points (59 studied populations). The scale with intervals of the polymorphism variant frequency values ​​(in %) is shown on the right. The Surfer software package (GoldenSoftware, LLC) (www.goldensoftware.com) was used to visualize the distribution of the rs1421085-C allele frequency in geographic space.

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3. Fig. 1. The relationship between January temperature (TEMP – abscissa axis) and the frequency of the rs1421085-C variant in the indigenous populations of Siberia (FREQ – ordinate axis). Spearman's rank correlation coefficient r = –0.439, P = 0.244. The STATISTICA 10 software package (StatSoftInc.) was used for the correlation analysis.

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4. Fig. 2. The relationship between July temperature (TEMP – abscissa axis) and the frequency of the rs1421085-C variant in the indigenous populations of Siberia (FREQ – ordinate axis). Spearman's rank correlation coefficient r = 0.506, P = 0.293.

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5. Fig. 3. Relationship between January temperature (TEMP – abscissa axis) and the frequency of the rs1421085-C variant in world populations (FREQ – ordinate axis). Spearman’s rank correlation coefficient r = –0.416, P = 0.00275.

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