Objective: The purpose of this study was to establish the occurrence of the Trp64Arg polymorphism of beta3 adrenergic receptor in non-obese women with PCOS.
Materials and Methods: This cross-sectional study was performed on 100 women with PCOS and normal women as the control group in Imam Khomeini Hospital of Tehran in 2016-2017. Peripheral blood sample (2 cc) was obtained from two groups for genomic DNA based on the gene bank. Polymorphisms were genotyped by of using ADRB3 Trp64Arg. Then the DNA was extracted by genomic kiagen kit. The primer was analyzed for PCR based on gene bank by using Primer3 software and then confirmed by primer Blast tool at NCBI site to conformity to the beta-3 adrenergic receptor gene. The protein changes were assessment by the Clastal W software.
Results: The sequence analysis presented in NCBI, transcript variant 1, with the code NM_000025.2, shows changes in the amino acid sequence of exon 1 in women with PCOS. Polymorphism in the codon 64 encoding the amino acid tryptophan (W) occurred in the nucleotide c.T190C, which changed the nucleotide T to C and then the amino acid sequence of the tryptophan was altered to arginine pW64R.
Conclusion: T-C polymorphism is evident in the codon 64 of the adrenergic β3 receptor in patients with PCOS. Therefore, Beta3 adrenergic receptor gene polymorphism (Thr164Ile) associates with this syndrome in nonobese women.
Methods: We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.
Results: PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.
Conclusion: Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.
OBJECTIVES: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults.
METHODS: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0-0.64), second (PRS 0.65-3.59), and third (PRS 3.60-8.18) tertiles.
RESULTS: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11-4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048).
CONCLUSION: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.
AIM OF THE STUDY: This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents.
MATERIALS AND METHODS: Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 μM). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and Methylene blue (MB 10 μM), sGC inhibitors; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 μM) a nitric oxide synthase (NOS) inhibitor; atropine (10 μM), a cholinergic receptor blocker; indomethacin (10 μM), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.
RESULTS: SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (Rmax). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation.
CONCLUSION: This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and β-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.