Association of Gln27Glu polymorphism of the β-2- adrenergic receptor with preeclampsia (original) (raw)
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Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor
International Journal of …, 2002
Objectives: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. Methods: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: A significant association was found between Gln27Glu substitution and preterm labor (Ps0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; Ps0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. Conclusion: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.
American Journal of Reproductive Immunology, 2012
We investigated genetic polymorphisms to understand the etiology of preterm delivery, which involves inflammatory cytokines and uterine contraction. Maternal polymorphisms of ADRB2, iNOS, and eNOS were examined, and associations between these and the risk of preterm delivery were sought. Method of Study This study was performed on 166 Korean women who underwent preterm delivery and 289 normal controls. Logistic regression analyses were carried out to identify single genes and haplotypes that affect the risk of preterm delivery. Results The G/G haplotype of ADRB2-rs1042713 and-rs1042714 was found to be associated with the risk of preterm delivery (OR = 1.90, 95% CI = 1.08-3.33, P-value = 0.0252). The genotype frequency of G allele in ADRB2-rs1042714 was associated with increased the risk of preterm delivery. However, after the adjustment of multiple comparison corrections, the association with preterm delivery was not remained significantly. Conclusion These findings possibly aid our understanding of the pathogenesis of preterm delivery and suggest that a haplotype with variants in maternal genes involved in adrenergic activation may lead to the dysregulation of uterine contractility and increase the risk of preterm delivery.
2019
Preeclampsia (PE), a pregnancy specific vascular disorder which is characterized by hypertension and proteinuria is a leading cause of maternal, fetal/neonatal morbidity and mortality affecting 5-14% of pregnancies. PE is a multifactorial disorder associated with poor placentation, placental hypoxia, poor angiogenesis and excessive maternal inflammation. Adrenomedullin (ADM) is a multifunctional peptide, plays an important role in the establishment and maintenance of healthy pregnancy, prevents an immune attack at peri-implantation period, vasodilation and promotes angiogenesis. In the present study, we enrolled a total of 600 subjects which includes 300 PE patients and 300 healthy pregnant women from South India to analyse two functional polymorphisms (rs4399321A/G and rs4910118C/T) of ADM gene. The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (p=0.02 and p=0.03). Individuals carrying the AA genotype of rs4399321A/G were s...
Gene, 2014
The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A polymorphism with susceptibility to preeclampsia was studied in 252 women consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166 A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and 48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%, respectively). The presence of G allele was associated with 1.69-fold increased risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and diastolic blood pressures in the presence of GG+GA genot...
β2-Adrenergic receptor genotype and preterm delivery
American Journal of Obstetrics and Gynecology, 2002
Our purpose was to determine whether the functional genetic polymorphisms of the β 2-adrenergic receptor (β 2 AR) that result in changes in amino acid residues 16 and 27 are associated with preterm delivery. STUDY DESIGN: A case-control study comparing the distribution of β 2 AR genotype between 251 Hispanic women delivered at term and 28 Hispanic women delivered preterm. Preterm delivery was defined as spontaneous onset of labor resulting in delivery before 37 weeks of gestation, in a singleton pregnancy, with no apparent etiology for preterm labor and delivery. Genomic DNA was isolated from peripheral blood, and β 2 AR alleles were identified by established techniques. RESULTS: Only one woman (4%) with preterm labor was homozygous for Arg16 versus 79 (31%) in the control group (P = .01, odds ratio 0.08). There was no association of preterm labor with genotype at position 27. CONCLUSION: Our data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the β 2 AR, protects from preterm delivery.
BMC Medical Genetics
Background: Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia. Methods: A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted. Results: Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98-10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15-10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77-113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09-0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16-11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D′ = 1, r 2 = 0.012). Conclusions: Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.
Saudi Journal of Biological Sciences, 2014
There are no earlier studies that reported the association of the 12Glu9 polymorphism in the alpha-2B adrenoceptor (ADRA2B) gene with gestational diabetes mellitus (GDM). We examined the potential association between the ADRA2B gene insertion/deletion (I/D) polymorphism in the Saudi population with GDM. Pregnant women with GDM have been reported to exhibit the same susceptibility as that observed in type 2 diabetes mellitus (T2DM). We have selected I/D polymorphism of the ADRA2B gene located in chromosome 2q11.1 that has been extensively related to T2DM and cardiovascular diseases. This case-control study was conducted with 200 GDM and 300 non-GDM pregnant women. Genotyping of I/D polymorphism was performed by conventional PCR method. Biochemical analyses were found to be significantly different between GDM and non-GDM subjects (p < 0.05). Genotype (ID + DD vs II, p = 0.0002) and allele (D vs I, p = 0.0002) frequencies of the 12Glu9 polymorphism were found to be statistically significant. However, a significant difference was found between allele and genotypes of I/D polymorphism of the ADRA2B gene or the clinical characteristics of the subjects. Our results obtained in this study indicate the ADRA2B gene in the Saudi women was associated with the development of GDM. ª 2014 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Metabolism, 2006
Gestational diabetes mellitus (GDM) is considered an important risk factor for the development of type 2 diabetes mellitus. We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and b 3-adrenergic receptor (ADRB3 Trp64Arg, b 3-AR) gene mutations, considered potential modifying factors in the etiology of type 2 diabetes mellitus. We evaluated the 2 gene mutations in late gestation in 627 pregnant women, all studied using the glucose challenge test, followed (in positive tests) by the oral glucose tolerance test (100 g, Carpenter and Coustan [J Obstet Gynecol. 1982;144:768-773] criteria) We diagnosed 309 women with GDM, 41 with gestational impaired glucose tolerance and 277 normal pregnant women. Age, family history of diabetes, prepregnancy body mass index, weight gain during pregnancy, plasma glucose levels, hemoglobin A 1c , islet autoantibody levels, and insulin treatment during pregnancy were all evaluated. All pregnant women were genotyped for IRS-1 (Gly972Arg) and b 3-AR (ADRB3 Trp64Arg) polymorphisms. The frequency of IRS-1 gene polymorphism was significantly higher in women with GDM than in women with a normal glucose tolerance (NGT) (P = .039), and there was a significant trend (P = .032) in the increasing frequency of mutant allele Arg from NGT N gestational impaired glucose tolerance N GDM. The search for b 3-AR gene polymorphism showed no significant differences between women with GDM and women with NGT. The X-Arg genotype of IRS-1 was significantly associated with a positive family history of diabetes in NGT (P = .006) and neared significance in GDM (P = .057). Moreover, we found that NGT carriers of both polymorphisms had a higher prepregnancy body mass index than carriers of the IRS-1 variant alone (P = .0034), the b 3-AR variant alone (P = .039), or neither (P = .048), suggesting a possible synergistic effect of the 2 gene polymorphisms. These results suggest that the IRS-1 genetic polymorphism is involved in the occurrence of gestational diabetes, as well as type 2 diabetes mellitus.
The Medical journal of Malaysia, 2012
Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.
2012
Polymorphisms within the β2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.