Page 46 - GTM-2-2

Global Translational Medicine FTO gene and obesity

ratio of body weight in kilograms to the square of height to an excessive weight gain. However, an association of these
in meters (kg/m ). BMI is the most convenient measure polymorphic variants with obesity requires clarification for
2
for determining the level of obesity and overweight in each specific population.
a population, since it is the same for both sexes and At present, much attention is paid to the prevention of
all age categories of adults. However, BMI should be obesity, which includes a normalized diet, higher level of
considered an approximate criterion due to the fact that in physical activity, and maintenance of a healthy lifestyle.
different people it may correspond to different degrees of Molecular genetic diagnostics will make it possible to
completeness.
identify individuals with an increased risk for obesity so
According to the World Health Organization (WHO) that preventive measures can be taken in a timely manner.
recommendations, a diagnosis of “overweight” or One of the most significant predictors of obesity is the
“obesity” in adults should be made based on these criteria:
(i) Overweight if BMI is equal to or more than 25; (ii) obesity FTO gene (a fat mass and obesity-associated gene) encoding
if BMI is equal to or more than 30. High BMI significantly the Fe(II)/2-oxoglutarate-dependent demethylase, which
increases the risk of cardiovascular diseases, metabolic is the ninth AlkB family protein found in mammals
[8]
syndrome, diabetes mellitus, etc. Morbid obesity reduces life (also called ALKBH9) and involved in the regulation
[2]
expectancy by about 7 years in women and 6 years in men . of metabolic rate, energy balance, thermogenesis, and
control over adipocyte differentiation into brown or white
According to 2016 data, 39% of the world’s adult fat cells .
[9]
population over 18 years old (39% of men and 40% of
women) was overweight and about 13% of adults (11% The human FTO gene is located on the chromosome
[3]
of men and 15% of women) were obese . Unfortunately, 16q12.2 with a total length of 410,50 kb, including nine
there has always been a persisting upward trend in the exons and eight introns and is extensively expressed in
number of overweight people. Previously, a big population the adipose tissue and the skeletal muscles of human
of obese patients was used to be a characteristic of with the highest expression in the hypothalamus, in the
developed countries with a high income per capita, but region that controls energy balance. In the genome-wide
this phenomenon has recently become more apparent in association study (GWAS) performed by Frayling et al.
low- and middle-income countries. According to the WHO, in 2007, the FTO gene was found to be able to influence
[10]
the number of overweight children under 5 years old has the risk for Type 2 diabetes development . It was shown
increased by 24% in Africa compared to that in 2000 . that A allele homozygous carriers of the FTO rs9939609
[4]
polymorphic variant had an average weight of 3 kg, and
If the mass of fat consumed exceeds the body’s ability to the risk for obesity was 1.67 times higher than that of T/T
oxidize it, obesity develops and progresses. Saturated fatty homozygotes . Further studies identified a large number
[10]
acids excessively supplied with food have a tendency to of polymorphic variants in the FTO gene associated not
cause structural changes in cell membrane phospholipids only with an increased body mass index [11-15] , but also
and disruption in the expression of genes that control with other metabolic conditions, such as increased levels
the conduction of insulin signal into the cell. In addition, of fasting insulin, glucose, triglycerides, and low levels of
fats are more caloric than proteins and carbohydrates: 1 g high-density lipoproteins .
[16]
of fat contains 9 kcal; 1 g of proteins and carbohydrates
contains 4 kcal each . Therefore, with the same volume, Obese (or overweight) single-nucleotide polymorphisms
[5]
fatty foods give the body twice as many calories as protein (SNPs) in the FTO gene were replicated in large European
and carbohydrate foods. populations [17,18] . According to the 1000 Genomes Project
data, significant differences in the frequencies of minor
Apart from overeating, lack of physical activity is
another important environmental factor contributing alleles for some polymorphisms were noted depending
on the population (Figure 1). For instance, the minor
to obesity development. Low physical activity leads to a allele frequency of the rs9939609 polymorphic variant
slowdown in the lipolysis and utilization of triglycerides
in the muscle and adipose tissue , as well as a decrease among Europeans is 34 – 44%, among Asians 11 – 20%,
[6]
among Spaniards 31 – 37%, and about 17% among South
[7]
in the translocation of glucose transporters in muscles , Americans . In our study, the minor allele frequencies of
[12]
which results in overweight and obesity. The development the polymorphic variants tested correspond to Europeans.
of obesity may be caused by a combination of excessive
food intake, lack of physical activity, and a hereditary The present study aimed to identify an association
predisposition to it. Studies of the genotypes of obese between 13 polymorphic variants of the FTO gene (Table 1)
individuals allowed identifying a number of polymorphic and obesity risks in the representatives from the Belarusian
variants of genes that contribute to a genetic predisposition population.

Volume 2 Issue 2 (2023) 2 https://doi.org/10.36922/gtm.352