Shelest B.A., Kovaleva Yu.A., Brek V.V. FTO GENE POLYMORPHISM IN HYPERTENSIVE PATIENTS WITH COMORBID PATHOLOGY

*228316*

PhD Shelest B.A., PhD Kovaleva Yu.A., PhD Brek V.V.

Kharkiv National Medical University, Kharkiv

FTO GENE POLYMORPHISM IN HYPERTENSIVE PATIENTS WITH COMORBID PATHOLOGY

The detection and prevention of hypertension associated with comorbid pathology is a currently central problem worldwide, since morbidity and mortality due to this pathology occupy a leading position in the world. In recent years, the number of people suffering from obesity has increased in economically developed countries. 2/3 of the population only in the US has an overweight, not to mention obesity [1].

It maybe said that obesity acquires features of a non-infectious epidemic, and it begins with childhood [2]. Abdominal obesity is often observed in adults, especially in women [3]. It has long attracted the attention of researchers as an independent risk factor and especially it’s interaction with hereditary factors. It is known that obesity leads to insulin resistance, diabetes mellitus type 2, dislipoproteinemia [4]

Having studied the mechanisms of the development of obesity and having determined, in particular, its genetic characteristics, it is possible to identify risk groups and develop preventive measures. In recent years, a gene associated with overweight and obesity has been discovered in full-scale studies. There are convincing data on its several structural polymorphisms, in particular rs9939609, associated with fat mass and obesity. Although such work remains quite small and the results of several studies remain rather contradictory.

The aim of the study was to investigate the FTO gene rs9939609 polymorphism in patients with arterial hypertension with comorbid pathology.

Material and methods. There were 325 people enrolled in the study, 135 men (41.54%) and 190 women (58.46%), the average age of patients was 62.4 ± 5.7 years.

All participants signed informed consent. All patients underwent the following examinations:

− Questioning (questionnaire included passport data, analysis of lifestyle, heredity, concomitant pathology and drug therapy);

− Anthropometry: measurement of height, body weight, waist circumference (WC), hip circumference (HC), calculation of body mass index (BMI);

− Measurement of blood pressure (BP) and heart rate (HR);

− Screening of biochemical panel: glucose, high-density lipoprotein cholesterol (HDL cholesterol), total cholesterol (TC), triglycerides (TG);

− Determination of single nucleotide polymorphism (SNP) rs9939609 FTO gene.

The body weight was evaluated by the body mass index according to WHO recommendations. The optimal BMI was 18.5-24.9 kg/m2, overweight is the BMI 25‑29.9 kg/m2 and the obesity was more than 30.0 kg/m2. In addition to body weight and height, attention was paid to the waist to hip ratio, and the type of fat distribution was established [3].

The determination of the FTO gene polymorphism was performed by real-time polymerase chain reaction (PCR) using Applied Biosystems allele-specific primers (rs9939609) on the 7500 Real Time PCR System thermocycler. Amplification was carried out in a final volume of 25 μ the reaction mixture. A set of reagents for conducting PCR-PB from Synthol was used for amplification, whereas allele-specific primers with a fluorescent probe were from Applied Biosystems. Thus, the reaction mixture included 2 μl of genomic deoxyribonucleic acid (DNA); 2.5 μl dNTP; 2.5 μl of MgCl2; 2.5 μl of 10 × PCR buffer B; 0.2 μl of Taq DNA polymerase; 1.25 μl of 20x allele-specific primer and fluorescent probe solution (Applied Biosystems) and 14.05 μl H₂0.

Biochemical studies of lipids included the determination in plasma of total cholesterol, TG, and HDL cholesterol by an enzymatic method using sets of the firm DIAKON-DS (Russia).

Considering that the distribution of quantitative quantities in all groups was close to normal, we used parametric methods. The critical value of the significance level p was chosen to be 0.05. During the sample analysis, qualitative and quantitative indicators were estimated using absolute and relative (in percent) frequencies. The central regularity and variability of the quantitative indicators were calculated by bringing the average of the arithmetic mean (M) and the standard deviation (m), the results represented as the expression: M ± m. The statistical hypothesis that there were no differences between two comparable groups was tested using the appropriate version of the Student's test (for dependent or independent samples). Mathematical calculations were carried out in Statsoft Statistica 6.0.

Results and discussion:

The prevalence of genotypes of the FTO gene in the examined patients was: AA - 17.5%, TA - 46.4%, TT - 36.1%.

In the course of the study, a correlation was revealed between the AA genotype of the FTO gene and the body weight. Thus, among the examined men and women in patients with AA genotype, the body weight was significantly higher ‑ 96.4 kg, compared with patients with TA and TT genotypes - 93.6 and 92.7 kg, respectively (p> 0.1). In addition, there was a tendency for increasing in BMI that made up 30.8 ± 0.5 kg/m² for genotypes of AA carriers, and for TA and TT carriers, 29.7 ± 0.6 and 29.5 ± 0, 8kg / m², respectively (0.1 <p> 0.05) (Table).

Parameters in hypertensive patients with comorbid pathology, in according to different FTO gene genotypes

Indicators	АА	ТА	ТT	р
Body weight, kg	96,4±2,3	93,6±2,1	92,7±1,9	> 0,1
Body mass index, kg / m2	30,8±0,5	29,7±0,6*	29,5±0,8*	> 0,1
Glucose, mmol / l	5,8±0,2	5,3±0,3*	5,2±0,4*	> 0,05
Patients with AH,%	71,3%	66,5%	64,7%
Patients without AH.%	33,4%	35,7%	36,3%
Patients with abdominal obesity,%	79,7%	69,2%	68,3%
Patients without abdominal obesity,%	23,6%	25,4%	24,9%

Notes: * - the degree of reliability with AA approaches (0,1<р>0,05).

When analyzing the relationship between rs9939609 of the FTO gene and the parameters of carbohydrate metabolism, it was established that patients with AA genotype had the blood glucose level significantly higher than patients with TA and TT genotypes: 5.8; 5.3 and 5.2 mmol / l, respectively (0.1 <p> 0.05) (Table 1).

Waist circumference in men with AA genotype was 102.6 ± 1.4 cm, and men with TA and TT genotype have 98.8 ± 1.1 and 97.7 ± 0.8 cm, respectively (p <0, 05 in comparison with the AA genotype). Males with AA genotype in comparison with men of TA and TT genotype have HC of 110.7 ± 1.3; 108.6 ± 1.2 and 107.8 ± 1.1 cm, respectively (p> 0.1). In the group of women, these differences also did not reveal reliability.

When analyzing a group of patients with different genotypes, it was found that among patients with AA genotype, patients with abdominal obesity were significantly more likely than among patients with other genotypes: 79.7% compared to 69.2% (TA genotype) and 68.3% (TT genotype), respectively (p <0.05). In addition, in patients with the FTO gene AA genotype, patients with a high blood glucose level were significantly more frequent: 36.4% (AA genotype), 31.1% (TA genotype) and 32.5% (TT genotype) (p> 0.1). In the group of patients homozygous for A allele, there was a tendency to increase the proportion of patients with AH in comparison with patients with other genotypes: 68.3% versus 63.4% (TA genotype) and 58.7% (TT genotype) (p> 0.1 ).

Сonspicuous is the fact that, the proportion of patients with low HDL cholesterol in the group of patients homozygous for A allele (≤ 1.30 mmol / L for women and ≤ 1.05 mmol/l for men) was significantly less than in the group with TT genotype: 52.4 and 55.3%, respectively (p <0.05), also in this group there was a tendency to decrease the number of patients with elevated TG level (≥ 1.5 mmol / l), in comparison with patients with TA and TT genotype: 33.7; 37.3 and 37.7%, respectively (p> 0.1).

Conclusions. It is important to allocate an additional group of genetic risk among patients already at risk for developing cardiovascular pathology, for which recommendations for weight control will avoid the development of other undesirable consequences.

LITERATURE:

1. Ogden C.I., Caroll M.D., Curtin L.R., McDowell M.A., Tabak C.J., Flegal R.M. Prevalence of overweight and obesity in the United States, 1999-2004 // J.Am. Med. Assoc. – 2006. – Vol.295, N13. – P.1549-1555

2. Nossain P., Kawar B., El Nahas M. Obesity and diabetes in the developing world – a growing challenge // N.Engl.J.Med. – 2007. – Vol.356, N3. – P.973-973 - ,5 – 2005

3. Obesity in cardiologist and endocrinologist practice / O.M. Bіlovol, O.M. Koval'ova, S.S. Popova, O.B. Tveretinov – Ternopіl': TDMU «Ukrmedkniga». ‑ 2009. ‑ p.300-301 [Ukrainian]

4. Belyaeva O.D., Berezina A.V., Bazhenova E.A. et al. Prevalence and forms of the metabolic syndrome in patients with abdominal obesity - in population of St.Peterburg // Arterial hypertension [Arterialnaya Hyper tenziya]. – 2012. – Vol.18, N3. – P.234-242 [Russian]