Związek składowych zespołu metabolicznego z genotypami polimorfizmu C825T w genie dla podjednostki B3 białka G (GNB3)

Lyudmyla N. Prystupa, Irina O. Moiseyenko, Victoria. Yu. Garbuzova, Vladyslava V. Kmyta, Irina A. Dudchenko

Sumy State University, Sumy, Ukraine

 

Abstract

Introduction: All components of the metabolic syndrome (MS) are the risk factors for the cardiovascular diseases, and their combination a great deal accelerates and complicates development of the diseases. Phenotypic expression of MS depends on the interaction of genetic and environmental factors.

The aim: The aim is to study the association of metabolic syndrome components with the genotypes of the C825T polymorphism in the GNB3 gene, which allows predicting the risks and determining individual lifestyle and treatment program for the future.

Materials and methods: The patients were analyzed for anthropomorphic data and abdominal obesity. Presence of MS criteria was assessed in the patients in accordance with the consensus of International Diabetes Federation (2009). Hypertension diagnosis is based on the recommendations of adapted Clinical Practice Guidelines “Arterial Hypertension” (2012). The study of the С825Т polymorphism in the G protein β3-subunit gene was conducted at molecular-genetic research laboratory of Sumy State University with subsequent analysis of restriction fragment length polymorphism. The data were statistically processed using SPSS Statistics 21.0 program on PC.

Results: T-allele carriers had 1.6 times higher risk of obesity than C-allele homozygotes ( р=0.034). Т825Т genotype carriers were 2.7 times higher risk of hypertension compared the carriers of С825С genotype of the С825Т polymorphism of the GNB3 gene (  р = 0.002). The risk of increased LDL cholesterol level in the minor allele carriers is 3.9 times higher than that in the major allele carriers. ( р = 0.002).

Conclusions: The results of our study concerning the association of the minor allele and T825 + C825T genotypes with the risk of components of the MS.

 

Wiad Lek 2018, 71, 7, -1249

 

Introduction

Doctors of different specialties often have to deal with various comorbid conditions. The most frequently occurring combination of disorders and conditions observed in the patients after 40 years of age is the combination of obesity, arterial hypertension, dyslipidemia, and carbohydrate metabolism impairment, though this combination has recently begun to affect a younger population [1, 2]. All these states were proposed to be combined by the term (MS). Almost all components of the MS are the risk factors for the cardiovascular diseases, and their combination a great deal accelerates and complicates development of the diseases [3]. Phenotypic expression of MS depends on the interaction of genetic and environmental factors [4]. For MS identification the criteria of WHO and International Diabetes Federation are used [5]. BMI was calculated according to the Quetelet index.

Distribution analysis of С825С, С825Т, and Т825Т genotypes showed a statistically significant difference between the experimental group and the control group (р<0.001 by χ2test).

The presence of MS increases the early hospital mortality rates and worsens the long-term prognosis [6, 7]. Major danger is represented by summation of different MS components, since they have a synergistic effect and form the pathogenetic circular mechanism that determines future fatal and non-fatal cardiovascular events [8].

The pathogenesis of MS is a rather complicated issue, but most researchers tend to think that it is abdominal obesity and related disorders of carbohydrate and lipid metabolism that provide the basis of MS [9].

Development of MS correlates with the genetic determination of muscle fibers composition, distribution of adipose tissue, activity and insulin sensitivity of the main enzymes of carbohydrate and fat metabolism. The development of MS is assumed to be associated with the genes encoding apolipoprotein AV (APO A5), membrane-bound fatty acid transporter CD36 (FAT), intestinal-type fatty acid-binding protein (FABP2), microsomal TG transfer protein (ATGL), adiponectin (ADIPOQ), adiponectin receptors type 2 (ADIPOR2) and G protein β3-subunit (GNB3).

G-protein is attached to the inner surface of the cell membrane and specifically changes its spatial configuration when interacting with a chemical compound molecule that catalyzes the formation of cAMP from ATP, which activates intracellular enzymes, transport processes and metabolism. This, the signal is transmitted from the plasma membrane to the intracellular structures [10].

Guanine nucleotide-binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. Ligand binding to heptahelical receptors results in the dissociation of the heterotrimeric G protein into Gα-GTP and Gbγ complexes, resulting in various cellular functions. Because of their crucial role in the function of many types of cells, genetic abnormalities in G protein subunits have the potential to be involved in the etiology of a wide range of clinical conditions.

The entire nucleotide-binding protein beta polypeptide 3 (GNB3) gene that is located in chromosome 12p13 spans 7.5 kb and is composed of 11 exons and 10 introns. In GNB3, polymorphism C → T (rs5443) at nucleotide number 825 in exon 10 of the b3 subunit of pertussis toxin-sensitive Gi type protein has been identified. This polymorphism induces the occurrence of a splice variant in which the nucleotides 498–620 of exon 9 are deleted. This deletion causes the loss of 41 amino acids of exon 9 along with the fourth Trp–Asp (WD) of the seven WD repeats that form a propeller structure [11, 12]. As the result, this mutation leads to synthesis of a β3-subunit form which lacks 41 amino-acid residues, but is more active functionally; in its turn it causes an increase in the intracellular calcium concentration, activation of a sodium-proton pump (SPP), an increase in intracellular signaling, and, as a consequence, an enhanced cellular response to hormonal stimulation [13, 14]. Related studies explained that increased intracellular calcium concentration and SPP activation as well as subsequent more rapid intracellular response are due to genetically fixed enhanced G-protein activation [12, 15, 16, 17, 18]. Thus, G-protein is involved into signal transduction from many growth factors and hormones that have a stimulating effect on the development of hypertrophic changes in the cardiovascular system [19]. Study of the skin lymphoblastic and fibroblastic cell lines with increased signal transduction showed a greater propensity to proliferation [20].

A number of studies have shown that T-allele carriers (patients with T825T and C825T genotypes) had a tendency to the spasm of coronary arteries (due to increased concentration of Ca++) and vessels of the microcirculatory bloodstream during administration of catecholamines, endothelin and angiotensin II [21, 22, 23, 24], which is indicative of hyperreactivity of the vascular bed. In addition, increased SPP activity in the renal tubules may lead to increased reabsorption of Na+ ions in the distal tubules and cause volume overload. Another possible mechanism of the pathological process may be represented by the tendency of T-allele carriers to obesity, which is one of the important factors contributing to the development of hypertension [25, 26, 27].

This became a theoretical justification of the hypothesis about the role of G-protein structural organization in the development of MS components. According to literature data, CAD mortality among MS patients is 23 times higher than in the general population. Therefore, early diagnosis of MS is the prevention or postponing of manifestation of type 2 diabetes and atherosclerotic vascular disorders [28].

Nowadays there is no consensus as for the underlying cause of metabolic disorders in the pathogenesis of MS. Some authors suppose that this is a hereditary predisposition to insulin resistance and obesity along with low physical activity. Compensatory hyperinsulinemia at first reduces sensitivity, and then blocks insulin receptors; as a result, ingested glucose and fats are deposited by adipose tissue. This further enhances insulin resistance. On the other hand, hyperinsulinemia suppresses the breakdown of fats, which contributes to the progression of obesity [12].

The Aim

Aim is to study the association of metabolic syndrome components with the genotypes of the C825T polymorphism in the GNB3 gene, which allows predicting the risks and determining individual lifestyle and treatment program for the future.

Materials and methods

Genotyping for the С825Т polymorphism in the GNB3 gene was performed in 621 subjects (Ukrainians), who were divided into 2 studied groups: 481 patients with MS signs and 140 apparently healthy individuals. Among the subjects there were 211 women (44%) and 270 men (56%) aged 38−78 years, with median age (interquartile range) – 59 (52−64) years. The control group included 140 apparently healthy individuals: 78 women (56%) and 62 men (44%) aged 30–78 years, with median age (interquartile range) – 54 (43–64) years.

The patients were analyzed for anthropomorphic data (height, weight, body mass index (BMI)) and abdominal obesity (waist circumference (WC), hip circumference (HC), and their correlation).

Presence of MS criteria was assessed in the patients in accordance with the consensus of International Diabetes Federation (2009).

Hypertension diagnosis is based on the recommendations of adapted Clinical Practice Guidelines “Arterial Hypertension” (2012) and the unified protocol of the Ministry of Health of Ukraine (2016) according to the results of detailed clinical and instrumental examination of patients [29].

Objective signs of target organs impairment were present in all patients: hypertrophy of LV (by ECG and echocardiography data) was detected in 481 patients (100 %); generalized narrowing of the retinal arteries – in 211 patients (44 %); microalbuminuria and/or moderate increase in plasma creatinine concentration (in men > 115–133 mmol/l, in women > 107–124 mmol/l) – in 135 patients (28 %).

Among the examined patients, stage 2 hypertension was observed in 394 subjects (82 %) and stage 3 hypertension – in 87 subjects (18 %).

BMI was calculated according to the Quetelet index: body mass/ body height2 (kg/m2). The criteria for patient distribution with regard to BMI were consistent with the WHO recommendations: BMI = 18.5 to 24.9 kg/m2 was considered normal body mass, BMI = 25.0 to 29.9 kg/m2 – overweight, BMI > 30.0 kg/m2 – obesity. Waist measurement > 102 cm in men and > 88 cm in women was taken as abdominal obesity.

The lipid metabolism study included the measurements of total cholesterol, triglycerides, cholesterol of low-density (LDL cholesterol) and high-density lipoproteins (HDL cholesterol).Cholesterol, TG, HDL cholesterol, and creatinine were measured by means of Cobas Mira automatic biochemical analyzer (Switzerland). VLDL cholesterol concentration was calculated by the formula: VLDL cholesterol = TG/2.2. LDL cholesterol was calculated by the formula of W. T. Friedewald: LDL cholesterol = cholesterol – (VLDL cholesterol + HDL cholesterol).

To control carbohydrate metabolism, serum glucose was measured by means of a glucose oxidase method. Enzyme immunoassay was used to define the level of immunoreactive insulin in blood plasma using a kit of DRG Instruments GmbH (Germany). Insulin resistance was evaluated according to the HOMA criterion, which was calculated by the formula: insulin concentration (μU/ml) x fasting glucose (mmol/l) / 22.5. Insulin resistance was proved with HOMA values > 2.77.

The study of the С825Т polymorphism in the G protein β3-subunit gene was conducted at molecular-genetic research laboratory of Sumy State University (license of the Ministry of Health of Ukraine № 333438 АБ). DNA was extracted from the whole blood leukocytes using DIAtom DNA Prep 100 kit («Isogene», Russia), which was followed by polymerase chain reaction to identify the polymorphic region of GNB3 gene (rs5443) with subsequent analysis of restriction fragment length polymorphism.

The data were statistically processed using SPSS Statistics 21.0 program on PC. Quantitative data were analyzed using the median values with interquartile range (25-th and 75-th percentiles). Independent groups were compared for quantitative values by means of rank analysis of variance (ANOVA) and Student’s test. Description of nominal values was carried out in the form of relative frequencies of study subjects. Groups were compared for the nominal value using χ2test (Pearson’s test). The binary values (risk factors) were analyzed by means of the odds ratio (OR) with confidence interval (CI) and the statistical significance index (p < 0.05).

All participants provided a written consent to take part in the study. The study was conducted in compliance with the Declaration of Helsinki.

Results

Among the 481 patients, 154 (32%) were homozygous for the С-allele, 265 (55%) – heterozygous and 62 (13%) – homozygous for the Т-allele. Т-allele frequency in the experimental group was 0.4, С-allele frequency – 0.6. Among the apparently healthy individuals, 78 (56%) were homozygous for the С-allele, 53 (38%) – heterozygous and 9 (6%) – homozygous for the Т-allele. Т-allele and С-allele frequency constituted 0.25 and 0.75, respectively.

Genotype frequency analysis of the С825Т polymorphism in the GNB3 gene demonstrated that the distribution of С825С, С825Т, Т825Т genotypes in the control group was as follows: 56%, 38% and 6%. Genotype frequency in the MS group was: С825С – 31.6 %, С825Т – 55.5 %, Т825Т – 12.9 %

Genotype distribution for the С825Т polymorphism in the GNB3 gene is shown in Figure 1.

Distribution analysis of С825С, С825Т, and Т825Т genotypes showed a statistically significant difference between the experimental group and the control group (р<0.001 by χ2test).

Anthropometric characteristics of the studied Ukrainians with regard to the genotypes of the С825Т polymorphism in the GNB3 gene are shown in Table I

BMI values in the carriers of С825Т and Т825Т genotypes were higher by 6% and 9% than in those with С825С genotype (р = 0.058 and р=0.043 by χ2test). However, C825T and T825T genotype carriers had no difference in BMI values (p = 0.674 by χ2test). On the other hand, the examined patients obviously had the signs of grade 1 obesity. According to the WC measurements, abdominal obesity signs [30] were found both by European (2012) and American criteria (2013).

T-allele carriers had 1.6 times higher risk of obesity than C-allele homozygotes (OR=1.6, 95% CI=1,2- 2,0; р=0.034).

Further, we analyzed the correlation between SBP and DBP values and genotypes of the С825Т polymorphism in the GNB3 gene.

Blood pressure levels with regard to the genotypes of the С825Т polymorphism in the GNB3 gene are shown in Table II.

We found that Т825Т genotype carriers were 2.7 times higher risk of hypertension compared the carriers of С825С genotype of the С825Т polymorphism of the GNB3 gene (OR = 2.7; CI 1.43−5.29; р = 0.002).

According to the results of carbohydrate metabolism analysis (Fig. 2), it was proved that plasma glucose concentration in patients with different genotypes was significantly different (p = 0.038 by χ2test).

Thus, glucose concentration in Т825Т genotype carriers was higher by 22% than in С825С genotype carriers (р = 0.014 by χ2test). The difference between glucose values in С825Т and С825С genotype carriers equaled 10 % (р = 0.024 by χ2test). In addition, there was a tendency in the T-allele homozygotes towards the maximum increase of hyperinsulinemia in the fasted state; however, the difference was not significant (p = 0.252 by χ2test ).

Increased HOMA index in the T-allele carriers as compared with C-allele homozygotes confirms insulin resistance (p < 0.01 by χ2test).

It was proved that the risk of carbohydrate metabolism disorder in the minor allele homozygotes was 3.7 times higher than that in the C-allele homozygotes (OR = 3.7, CI 1.701−8.294; р = 0.001).

Levels of cholesterol, TG, LDL cholesterol, HDL cholesterol with regard to the genotypes of the С825Т polymorphism in the GNB3 gene are shown in Table III.

As is shown in Table III cholesterol concentration in the carriers of Т825Т genotype was higher by 24% and 20% than in those with С825Т and С825С genotypes (р = 0.001 and р = 0.019 Student’s test). The difference between cholesterol concentrations in С825С and С825Т genotype carriers was not significant (р = 0.082 Student’s test). TG concentration in Т825Т genotype carriers was higher by 37% than in С825С genotype carriers (р = 0.028 Student’s test). There was no observed difference in TG concentrations in С825Т carriers as compared to Т825Т and С825С genotype carriers (р = 0.184 and р = 0.074 Student’s test). LDL cholesterol concentration in Т825Т genotype carriers was higher by 24% and 21% as compared to С825Т and С825Т genotype carriers (р = 0.001 and р = 0.020 Student’s test). С825Т genotype carriers showed a tendency towards significantly higher LDL cholesterol concentrations as compared to С825С genotype carriers (р = 0.056 Student’s test).

Considering that LDL cholesterol is the most atherogenic fraction of lipids, we analyzed the distribution of genotypes of the C825T polymorphism in the GNB3 gene with regard to this parameter in patients with MS (Table IV).

As is shown in Table IV, there were 25.1 % more С825С genotype carriers among the patients with normal LDL cholesterol level than among those with increased LDL cholesterol level (р = 0.032 Student’s test); among the latter, Т825Т genotype was observed 2 times more often than С825С genotype.

The risk of increased LDL cholesterol level in the minor allele carriers is 3.9 times higher than that in the major allele carriers. (OR = 3.9, CI 1.56−10.27; р = 0.002).

Discussion

Obesity worsens the course of hypertension, increases the risk of early target organ complication that becomes the main cause of disability and mortality in this category of patients [31]. More than half of patients with hypertension have dyslipidemia, and only 10% of them reach normal parameters of lipid profile. The evidence base for genetically determined mechanisms of such MS components as hypertension, obesity, dyslipidemia, and carbohydrate metabolism disorders is increasing.

In this study, we demonstrated the difference in genotype distribution for the С825Т polymorphism in the GNB3 gene in the patients with MS. In addition, the obtained data show the association between the genotypes of the studied polymorphism and the components of MS.

The study of frequency of genotypes and alleles for the C825T polymorphism in the GNB3 gene in the group of apparently healthy individuals and in patients with MS is controversial. The results obtained in this study are consistent with the conclusions of Ye. V. Velitchenko et al. [32], A. V. Polonnikova et al. [33] and A. V. Benjafield et al. [34]. The researchers have demonstrated a higher T-allele frequency in healthy individuals and among patients with hypertension, which equaled 0.43 and 0.52 [23]. The results of our study concerning the association of the minor allele and T825 + C825T genotypes with the risk of hypertension are confirmed by the results of many researchers [35–41]. Our results contradict the study data of G. A. Kamiduliyeva et al., who establish the association of C-allele with hypertension [42]. No difference in the distribution of allelic variants, as well as no correlation between hypertension and the C825T polymorphism in the GNB3 gene were observed by I. A. Kabadou et al. (2013) and in the studies of 2013-2015 [40, 43, 44]. Genotyping performed in the residents of Chongqing (China) showed a significant difference in the frequency of genotypes for the C825T polymorphism in the GNB3 gene [45]. Other researchers studying the association of this polymorphism with hypertension in patients with rheumatoid arthritis could not prove it in T-allele carriers (OR = 0.92, CI 0.49–1.76; p = 0.813) [46].

The data obtained in the study of association between the C825T polymorphism in the GNB3 gene and body mass were consistent with the results of J. Y. Lee [47], Ch. Maniotis [48], but contradicted the data of G. Andersen [49], T. J. Hsiao [50], and G. A. Khamidullayeva [42]. BMI values in the carriers of С825Т and Т825Т genotypes were higher than in those with С825С genotype (р= 0.058, р = 0.043).

Studies of the association between obesity risks and the C825T polymorphism in the GNB3 gene are controversial, but the results of our study are consistent with the conclusions of A. Lyer et al. [51], A. Nejatizadeh et al. [52], N. Stefan et al. [53] and M. Yamamoto et al. [36]. We proved that the carriers of T-allele of the С825Т polymorphism in the GNB3 gene had 1.6 times higher risk of obesity than C-allele homozygotes (OR = 1.6, CI 0.810−3.164; р = 0.034), which was also demonstrated by the results of above-mentioned researches in population studies [36, 51−53]. European scientists studying the genetic factors of obesity in children and their parents conducted a concurrent experimental molecular genetic study and identified the role of the C825T polymorphism in the GNB3 gene in the molecular mechanisms of this pathology in children [54]. However, the results of other scientists’ studies did not confirm the dependence of obesity on alleles and genotypes of the C825T polymorphism in the GNB3 gene [49, 50, 53, 55].

Considering the effect of overweight and obesity on the development of hypertension, we found that the risk of hypertension in overweight and obese subjects with C825T and T825T genotypes was 2.2 times higher than that in C825C genotype carriers (OR = 2.22 CI 1.02–4.83; p = 0.04). Similar results were obtained by M. L. Grove et al. [26], who proved that the risk of hypertension in overweight and obese subjects with C825T and T825T genotypes of the С825Т polymorphism in the GNB3 gene was 2.7 times higher than that in C825C genotype carriers (OR = 2.71 CI 1.19−6.17; р = 0.02), as well as by E. Alioglu et al. [35] – (OR = 1.815, CI 1.565−2.106; p = 0.0001).

Since the action of insulin on cells is carried out using G protein-associated mechanism, a hypothesis has appeared stating possible influence of the investigated polymorphism on the development of diabetes. The cascade of intracellular reactions initiated by the increased activity of G protein, with the inclusion of adenylate-cyclase, protein kinase and glycogen phosphorylase mechanisms, leads to insulin resistance and increased liver glucose synthesis. Increased activity of G protein stimulates opening of calcium channels that in its turn affects insulin secretion [57, 58].

The results of our study demonstrated that glucose concentration in Т825Т genotype carriers was higher than in С825С genotype carriers.

J. Kiani et al. [59] in their study demonstrated a significant association of T-allele with diabetes, whereas T825T genotype carriers had the highest risk of carbohydrate metabolism disorder as compared to carriers of C825T and C825C genotypes. Greek researches obtained similar results [48]. In the study conducted by M. Yamamoto et al. [36], T-allele carriers did not have significant association with the development of diabetes. The results of analysis of 10 candidate genes did not demonstrate any association between the C825T polymorphism in the GNB3 gene and the development of diabetes [60]. The studies conducted by researchers in 2010-2011 revealed no association of the C825T polymorphism in the GNB3 gene with blood glucose or insulin [61, 62].

According to O. M. Pionova et al. [63], O. I. Mitchenko [64], O. M. Prystupyuk [65], patients with hypertension and high BMI have all atherogenic fractions of plasma lipids increased and HDL cholesterol concentrations decreased. This was confirmed by our study results, too. Thus, obese and overweight patients with hypertension had higher values of cholesterol and TG than patients with normal body mass (p = 0.001 and p = 0.026). Moreover, obese and overweight patients demonstrated higher values of LDL cholesterol (р = 0.002 and р= 0.001) and lower values of HDL cholesterol than patients with normal body mass (p = 0.001 and p = 0.022).

Analysis of correlation between lipid profile parameters and the C825T polymorphism in the GNB3 gene showed that Т825Т genotype carriers had higher cholesterol concentration as compared to С825Т and С825С genotype carriers (р = 0.001 and р = 0.019), higher TG level as compared to С825С genotype carriers (р=0.0828), higher LDL cholesterol level as compared to С825С and С825Т genotype carriers (р = 0.001 and р = 0.020). Similar data were obtained in the studies of Y. B. Kang et al. [66], X. Wang et al. [67], B. Saller et al. [68], but were not confirmed by the studies of Y. Suwazono et al. [69] and M. Choi et al. [70].

Conclusions

Thus, this study has proved the association of the C825T polymorphism in the GNB3 gene, namely T-allele in the genotype, with the risk of developing MS, namely its components: hypertension, obesity, carbohydrate and lipid metabolism disorders.

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This work was carried out in the framework of the research work «The role of allelic polymorphism of genes in the development of pathological processes and diseases» (registration number №0110U005038).

Authors’ contributions:

According to the order of the Authorship

Conflict of interest:

The Authors declare no conflict of interest

CORRESPONDING AUTHOR

Irina O. Moiseyenko

Sumy, Charkovskaya 23/21

tel: +38050231271

e-mail: irina.olegovna85@gmail.com

Received: 01.07.2018

Accepted: 17.09.2018

Figure 1. Genotype frequency of the С825Т polymorphism in the G protein β3-subunit gene in the experimental and control groups.

Table I. Anthropometric characteristics of the patients with arterial hypertension with regard to the С825Т polymorphism in the G protein β3-subunit gene

Value

Genotype

Body mass index, kg/m2

WC, cm

HC, cm

WC/HC,

relative units

С٨٢٥С

29.1 (24−31.9)

n = 154

100.7

(96.4−104.2)

105.4

(99.4−110.2)

0.9

С٨٢٥Т

31 (25.8−33.8)

n = 265

103.4

(99.6−106.6)

107

(102−111.2)

0.96

Т٨٢٥Т

32 (26−34)

n = 62

104

(99.8−107)

111

(107.4−120.2)

0.94

р χ2

p = 0.047

p = 0.649

p = 0.034

p = 0.544

 

Figure 2. Plasma glucose concentration with regard to the С825Т polymorphism in the G protein β3-subunit gene

Table II.Systolic and diastolic blood pressure levels with regard to the С825Т polymorphism in the G protein β3-subunit gene

Genotype

SAP

DAP

С٨٢٥С

164 (160−170)

100 (95−100)

С٨٢٥Т

170 (165−175)

105 (100−105)

Т٨٢٥Т

180 (175−185)

110 (110−115)

р

р = ٠.٠٤٦

р = ٠.٨٨١

Table III. Lipid profile values with regard to the genotypes of the С825Т polymorphism in the G protein β3-subunit gene

Value

Genotype

Cholesterol,

mmol/L

TG,

mmol/L

LDL cholesterol,

mmol/L

HDL cholesterol,

mmol/L

С825С

3.9

(3.2−4.6)

0.94

(0.74−1.52)

2.44

(1.56−2.76)

1.14

(0.95−1.2)

С825Т

4.1

(3.5–5.1)

1.21

(0.87−1.98)

2.54

(1.87−3.52)

1.09

(0.96−1.2)

Т825Т

5.1

(4.3−5.9)

1.5

(1.08−2.08)

3.2

(2.59−3.81)

1.14

(1.01−1.2)

р

0.003

0.044

0.002

0.522

Table IV. Genotype frequency of the С825Т polymorphism in the G protein β3-subunit gene with regard to the concentration of LDL cholesterol

Genotype

Patients with MS

Normal LDL cholesterol,

n = 346

Increased LDL cholesterol,

n = 135

n

%

n

%

С٨٢٥С

133

38.7

18

13.6

С٨٢٥Т

190

55

76

56.8

Т٨٢٥Т

23

6.3

41

29.5

Р

0,004

0,002