The article is devoted to the role of insertion-deletion polymorphism of -2-adrenoreceptor gene in development of hereditary disorders of cardiac conduction. We examined 71 patients with atrioventricular blocks and 92 patients with sick sinus node syndrome. Statistically significant preponderance of homozygous genotype DD of ADRA2B gene was found in both groups. Associations of alleles with male or female gender were also revealed.
Among adrenergic receptor subtypes that regulate lipid mobilization, the alpha2-adrenergic receptor is involved in the inhibition of fatty acid mobilization from adipose tissue. A C-1291G polymorphism is located in the alpha2-adrenergic receptor gene (ADRA2A) but no association with body fat accumulation has been reported yet.
Body mass index (BMI), fat mass (FAT), percentage body fat (%FAT), trunk-to-extremity skinfold ratio (TER), sum of eight skinfolds (SF8), and abdominal subcutaneous (ASF), visceral (AVF), and total (ATF) fat areas assessed by CT scan have been measured in adult sedentary white (n = 503) and black (n = 276) subjects participating in the HERITAGE Family Study. Association between the C-1291G polymorphism and each phenotype was tested separately in men and women of each race using ANCOVA with the effects of age as covariate in addition to the effects of BMI for TER and of FAT for AVF, ASF, and ATF.
The allele frequencies of the ADRA2A C-1291G polymorphism differed between races. No association was observed in white subjects, except for a moderate effect of the polymorphism accounting for less than 1% of the variance in AVF and ATF in women. In black subjects, however, the G-1291 allele was found to be associated with an increase of TER in men (3.8% of variance accounted for by the polymorphism), while in black women it was associated with a decrease in TER (2.9%) and in AVF (2.5%).
These results suggest a role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independently of total body fatness.
Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.
alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction.
This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years.
In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population.
The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.
Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the alpha2B-adrenergic receptor ( ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance.
We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline.
All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02-7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76-15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend).
The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.
The ADRA2B gene 301-303 I/D polymorphism is associated with various cardiovascular phenotypes. However, an association of genotypes with the timing structure of cardiac cycle remains unclear. The central hemodynamic parameters were assessed by pulse wave analysis in 63 residents of the Kola Peninsula (68 N) aged 27-65 yr. The genotypes were determined by PCR. The paired comparisons revealed that II genotype carriers had higher values of augmentation index ( P = 0.014), ejection duration ( P = 0.045), and lower SEVR ( P = 0.035) than DD homozygotes. Multiple regression analysis adjusted for age, body mass index, heart rate, and blood pressure confirmed these results. Further sex stratified analysis showed that the associations existed only in men ( n = 33) whereas in women ( n = 30) the differences were suggestive ( P
This study investigated the non-genetic and genetic risk factors for arterial hypertension (AH) in two ethnic groups living in the Mountain Shoria region: Shors and non-indigenous people.
Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older).
The prevalence of AH was lower in Shors (39.9% vs. 46.1%), mainly due to differences between men from the different groups: 33.2% vs. 45.8%. The percentage of people with AH, overweight, and obesity (including transabdominal obesity) in the different age groups did not differ between ethnicities. We identified statistically significant differences in the prevalence of hypertension according the two ethic groups according to age, body weight, and abdominal obesity. I/D ACE and ADRA2B polymorphisms were associated with AH. In DD ACE and DD ADRA2B carriers, there were fewer hypertensive patients in Shors than in non-indigenous people: 40.6% vs. 58.6% and 38.3% vs. 64.0%, respectively. In DD ACE carriers, more Shors had AH (60.0% vs. 37.1%).
Among Shors, the following factors increased AH risk: female sex, age, hypercholesterolemia, hyperbetacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), glucose intolerance, and the DD ACE, CT MTHFR, and AA ADRB1 genotypes; among the non-indigenous population, the main factors were age, hypercholesterolemia, hyperbetacholesterinemia, hypoalfacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), and ID ACE genotype.
The short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the alpha2B-adrenergic receptor gene was previously found to be associated with reduced basal metabolic rate in obese subjects. We investigated the effects of this polymorphism on changes in body weight in Finnish non-diabetic and type 2 diabetic subjects during a 10 y follow-up.
Controlled 10 y follow-up study with baseline, 5 and 10 y examinations.
A total of 126 non-diabetic control subjects and 84 newly diagnosed, middle-aged type 2 diabetic patients from eastern Finland participated.
Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and glycosylated hemoglobin A1c. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis.
No significant differences were found in the prevalence of the 12Glu9 deletion polymorphism between non-diabetic and type 2 diabetic subjects. The non-diabetic subjects with the Glu9/Glu9 genotype had a greater increase in their mean body weight during 5 y follow-up than the non-diabetic subjects with other genotypes (changes in body weight 0.4+/-5.7, -0.5+/-6.4 and 3.4+/-4.9% for the Glu12/Glu12, Glu12/Glu9 and Glu9/Glu9 genotypes, respectively, P=0.040 for the difference between the groups). Also, the trend for the increment of body weight was statistically significant in the non-diabetic subjects with the Glu9/Glu9 genotype (P=0.012). The 12Glu9 polymorphism was not cross-sectionally or longitudinally associated with body weight in type 2 diabetic subjects.
The genotype of two short alleles (Glu9/Glu9) was associated with an increase in body weight among non-diabetic subjects.
An association study was performed for genetic polymorphisms in ADRB3 (rs4994) and ADRA2A (rs1800544, rs553668) genes to estimate their effect on quantitative parameters, including glucose, insulin, and HOMA-IR index in women from the Tatar population of Russia. It has been shown that CT and CC are associated with metabolic syndrome and increased insulin. It was shown that ADRA2A (rs1800544) gene polymorphism was associated with high levels of insulin and an increased HOMA-IR index in GG- and GC-genotype carriers.
The sympathetic nervous system (SNS) is linked to glucose, lipid, and protein metabolism. The a2A -adrenergic receptor (ADRA2A) is involved in the SNS and mediates inhibition of insulin secretion and lipolysis. The association of ADRA2A single-nucleotide polymorphisms (SNPs) with obesity and/or type 2 diabetes (T2D) was investigated.
Genotyping was performed in a case-control study of 1,177 Swedish individuals, including lean and obese subjects with normal glucose tolerance (NGT) and T2D patients. ADRA2A mRNA expression was measured in pancreatic islets isolated from T2D patients and nondiabetic subjects.
SNP rs553668 was associated with T2D in men (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.08-2.01; P = 0.015) but this association was lost after adjusting for age and for body mass index (BMI). Associations were also detected when comparing obese NGT and lean NGT subjects (OR = 1.49; 95% CI = 1.07-2.07; P = 0.017), and in obese (OR = 1.62; 95% CI = 1.06-2.49; P = 0.026), but not in lean T2D. In women, multiple logistic regression regarding SNP rs521674 demonstrated an increased OR of 7.61 (95% CI = 1.70-34.17; P = 0.008) for T2D when including age as a covariant. Correcting for BMI removed the significant association. When age was included in the model, association also found when obese T2D patients were compared with lean NGT subjects (P = 0.041). ADRA2A mRNA expression in human pancreatic islets was detectable, but with no statistically significant difference between the diabetic and the control groups.
ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.
To estimate the prevalence of the genotypes of the candidate genes ACE (I/D, rs4646994), ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), MTHFR (C677T, Ala222Val, rs1801133), and eNOS (4b/4a) and their association with hypertension in two ethnic groups of Mountain Shoria.
A clinical and epidemiological study was conducted in a population compactly living in the hard-to-reach areas of Mountain Shoria (the settlements of Orton, Ust-Kabyrza, and Sheregesh of the Kemerovo Region). A continuous method was used to survey 1178 residents from the above settlements; the sample consisted of adults (aged 18 years and older), 565 people were genotyped.
The prevalence of hypertension among the population of Mountain Shoria was 42.3%. The incidence of this disease among the Shorians was lower (39.9%) than that among the representatives of non-indigenous people (46.1%). The ethnically justified peculiarities of the association of ADRA2B and ACE I/D polymorphisms with hypertension were established. There were fewer patients with hypertension among ACE ID and ADRA2B DD genotype carriers in the cohort of the Shorians than in that of the non-indigenous population: 40.6% versus 58.6% and 38.3% versus 64%, respectively. Conversely, there were more hypertensive patients among the carriers of the homozygous ACE DD genotype in the native ethnic group (60%) than in the non-indigenous one (37.1%).
Adverse prognostic ACE DD, ADRB1 AA, MTHFR TT, and eNOS 4a/4a genotypes were more frequently observed in the non-indigenous ethnic groups; the ADRA2B DD genotype was more common in the native population. Hypertension was associated with the ACE DD, ?THFR CT, and ADRB1 AA genotypes in the native ethnic group and with the ACE ID genotype in the non-indigenous population.