Effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and cardiovascular disease: A meta-analysis.

BACKGROUND AND AIM: The impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established correlation with diminished blood cholesterol levels. This meta-analysis aimed at exploring the effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and CVD. METHODS AND RESULTS: PubMed, Embase, and the Cochrane Library were searched for cohort and case-control studies published until October 1, 2023. The studies should report the association of the PCSK9 R46L genetic variant with one of the following: fasting plasma insulin, blood glucose levels, diabetes mellitus, and CVD risk. A dominant model of the PCSK9 R46L genetic variant was employed to statistical analysis. The meta-analyses were performed for continuous variables with standard mean difference (SMD), categorical variables with odds ratio (OR) using a random-effects model. A total of 17 articles with 20 studies engaging 1,186,861 population were identified and mobilized for these analyses. The overall results indicated that, compared with non-carriers of the PCSK9 R46L genetic variant, carriers of the PCSK9 R46L genetic variant did not increase or decrease the levels of fasting plasma insulin (3 studies with 7277 population; SMD, 0.08; 95% CI, -0.04 to 0.19; P = 0.270), and the levels of fasting plasma glucose (7 studies with 9331 population; SMD, 0.03; 95% CI, -0.08 to 0.13; P = 0.610). However, carriers of the PCSK9 R46L genetic variant indeed had 17% reduction in the risk of CVD (11 studies with 558,263 population; OR, 0.83; 95% CI, 0.71 to 0.98; P = 0.030), and 9% increase in the risk of diabetes mellitus (10 studies with 744,466 population; OR, 1.09; 95% CI, 1.04 to 1.14; P < 0.01). Meta-regression analyses indicated that the increased risk of diabetes mellitus and the reduced risk of CVD were positively correlated with reduction in LDL-C (P = 0.004 and 0.033, respectively). CONCLUSIONS: PCSK9 R46L genetic variant exhibited an elevated susceptibility to diabetes mellitus alongside a reduced vulnerability to CVD.

Effect of Intensive Lipid-Lowering Therapy on Coronary Plaque Stabilization Derived from Optical Coherence Tomography: a Meta-analysis and Meta-regression.

PURPOSE: The definitive impacts of intensive lipid-lowering therapy (LLT) on plaque stabilization and the relationship between the key markers during LLT and plaque stability remain unquestioned. Thus, these meta-analysis and meta-regression intend to holistically evaluate the influence exerted by rigorous LLT on the minimum fibrous cap thickness (FCT) and maximum lipid arc as discerned through optical coherence tomography (OCT). This study further scrutinizes the correlation of this impact with variations in high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), or additional parameters within patients diagnosed with coronary artery disease (CAD). METHODS: Comprehensive searches were conducted on platforms including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published until June 1, 2023. The search was language agnostic and targeted RCTs elaborating on the correlation between high-intensity statin therapy or statins used concomitantly with other lipid-lowering medications and the minimum FCT and maximum lipid arc as assessed by OCT. The meta-analyses were executed employing a standard mean difference (SMD) algorithm with random-effects on continuous variables. These methodologies align with the Preferred Reporting Items for Systematic and Meta-analysis (PRISMA) guidelines. RESULTS: A spectrum of 12 RCTs engaging 972 patients were identified and mobilized for these analyses. Meta-analysis outcomes depicted a conspicuous correlation between intensive LLT and an enhanced minimum FCT (12 studies with 972 participants; SMD, 0.87; 95% CI, 0.54 to 1.21; P < 0.01), reduced maximum lipid arc (9 studies with 564 participants; SMD, -0.43; 95% CI, -0.58 to -0.29; P < 0.01). Meta-regression analysis has determined an association of elevated minimum FCT with decreased LDL-C (ß, -0.0157; 95% CI, -0.0292 to -0.0023; P = 0.025), total cholesterol (TC) (ß, -0.0154; 95% CI, -0.0303 to -0.0005; P = 0.044), and apolipoprotein B (ApoB) (ß, -0.0209; 95% CI, -0.0361 to -0.0057; P = 0.022). However, no significant association was discerned relative to variations in hs-CRP/CRP (ß, -0.1518; 95% CI, -1.3766 to -1.0730; P = 0.772), triglyceride (TG) (ß, -0.0030; 95% CI, -0.0258 to -0.0318; P = 0.822), and high-density lipoprotein cholesterol (HDL-C) (ß, 0.0313; 95% CI, -0.0965 to 0.1590; P = 0.608). Subsequent subgroup meta-analysis demonstrated that high-intensity statin therapy (5 studies with 204 participants; SMD, 1.03; 95% CI, 0.67 to 1.39; P < 0.01), as well as a combinative approach including PCSK9 antibodies and statins (3 studies with 522 participants; SMD, 1.17; 95% CI, 0.62 to 1.73; P < 0.01) contributed to an increase in minimum FCT. Parallelly, high-intensity statin therapy (4 studies with 183 participants; SMD, -0.42; 95% CI, -0.65 to -0.19; P < 0.01) or the combined application of PCSK9 antibodies and statins (2 studies with 222 participants; SMD, -0.98; 95% CI, -1.26 to -0.70; P < 0.01) was evidenced to decrease the maximum lipid arc. CONCLUSIONS: Intensive LLT, mainly high-intensity statin therapy and combined PCSK9 antibody with statin, has a beneficial effect on coronary plaque stabilization derived from OCT in patients with CAD. Coronary plaque stabilization is primarily due to lipid-lowering effect, not anti-inflammatory effect. Moreover, the lipid-lowering effect has nothing to do with the changes in HDL-C and TG, but is mainly related to the reduction of LDL-C, TC, and ApoB.

Enhancing the Safety and Efficacy of PSMA-Based Small-Molecule Drug Conjugates by Linker Stabilization and Conjugation to Transthyretin Binding Ligand.

This work describes the enhancement of a novel antitumor therapeutic platform that combines advantages from small-molecule drug conjugates (SMDCs) and antibody drug conjugates (ADCs). Valine-citrulline (VCit) dipeptide linkers are commonly used cathepsin B cleavable linkers for ADCs. However, the instability of these linkers in mouse serum makes translating efficacy data from mouse to human more challenging. Replacing the VCit linker with glutamic acid-valine-citrulline (EVCit) has been reported to enhance the stability of ADCs in mouse serum. However, the effect of EVCit linker on the stability of SMDCs has not been reported. Here, we report that incorporating the EVCit linker in prostate-specific membrane antigen-targeting SMDCs, equipped with the transthyretin ligand AG10, resulted in conjugates with lower toxicity, an extended half-life, and superior therapeutic efficacy to docetaxel in a xenograft mouse model of prostate cancer. This should make SMDCs' preclinical toxicity and efficacy data from mice more reliable for predicting human results.

Adrenal Ablation Versus Mineralocorticoid Receptor Antagonism for the Treatment of Primary Aldosteronism: A Single-Center Prospective Cohort Study.

BACKGROUND: Superselective adrenal arterial embolization (SAAE) is an alternative treatment for patients with primary aldosteronism (PA). This single-center prospective cohort study aimed to compare the efficacy of SAAE with mineralocorticoid receptor antagonists (MRA) in treating patients with PA who refused unilateral adrenalectomy. METHODS: Of the 140 PA patients who were enrolled in the study and completed 12-month follow-up, 74 patients underwent SAAE and 66 received MRA treatment. The clinical and biochemical outcome was compared at 1, 6, and 12 months after the procedure. RESULTS: Baseline clinical and biochemical characteristics of the patients were similar between groups. Office, home, and ambulatory blood pressure reduction at 1 month after discharge was more pronounced in the SAAE group than MRA group (all P < 0.05) while the blood pressure reduction was comparable between the 2 groups at 6 and 12 months. Patients who underwent SAAE took less antihypertensive medications than the MRA group during 12-month follow-up (P < 0.01). Both SAAE and MRA treatment improved renin suppression, aldosterone-to-renin ratio elevation, and hypokalemia at 6 and 12 months, whereas only SAAE but not MRA reduced plasma aldosterone levels. Moreover, SAAE achieved higher rates of complete clinical and biochemical success than MRA (both P < 0.01). Logistic regression found that complete clinical and biochemical success was only directly associated with diagnosis of unilateral PA in contrast to bilateral PA (P < 0.01). CONCLUSIONS: The present study provides evidence that SAAE is a reasonable choice of treatment in patients with either unilateral or bilateral PA in terms of clinical and biochemical outcomes. This study was registered at Chictr.org.cn (ChiCTR2100045896).

Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects.

Several investigations into the sites of action of opioid analgesics have utilized peripherally acting mu-opioid receptor antagonists (PAMORAs), which have been incorrectly assumed to possess limited permeability across the blood-brain barrier. Unfortunately, the poor pharmacokinetic properties of current PAMORAs have resulted in misunderstandings of the role of central nervous system and gastrointestinal tract in precipitating side effects such as opioid-induced constipation. Here, we develop a drug delivery approach for restricting the passage of small molecules across the blood-brain barrier. This allows us to develop naloxone- and oxycodone-based conjugates that display superior potency, peripheral selectivity, pharmacokinetics, and efficacy in rats compared to other clinically used PAMORAs. These probes allow us to demonstrate that the mu-opioid receptors in the central nervous system have a fundamental role in precipitating opioid-induced constipation. Therefore, our conjugates have immediate use as pharmacological probes and potential therapeutic agents for treating constipation and other opioid-related side effects.

Omentin­1 induces osteoblast viability and differentiation via the TGF­ß/Smad signaling pathway in osteoporosis.

Osteoporosis is a bone­related disease that results from impaired bone formation and excessive bone resorption. The potential value of adipokines has been investigated previously, due to their influence on osteogenesis. However, the osteogenic effects induced by omentin­1 remain unclear. The aim of the present study was to determine the regulatory effects of omentin­1 on osteoblast viability and differentiation, as well as to explore the underlying molecular mechanism. The present study investigated the effects of omentin­1 on the viability and differentiation of mouse pre­osteoblast cells (MC3T3­E1) using quantitative and qualitative measures. A Cell Counting Kit­8 assay was used to assess the viability of MC3T3­E1 cells following treatment with different doses of omentin­1. Omentin­1 and bone morphogenetic protein (BMP) inhibitor were added to osteogenic induction mediums in different ways to assess their effect. The alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining of MC3T3­E1 cells treated with omentin­1 and/or BMP inhibitor were used to examine the effects of omentin­1 on differentiation and mineralization. Western blotting was used to further explore its potential mechanism, and to study the role of omentin­1 on the viability and differentiation of osteoblasts. The results showed that omentin­1 altered the viability of MC3T3­E1 cells in a dose­dependent manner. Omentin­1 treatment significantly increased the expression of members of the TGF­ß/Smad signaling pathway. In the omentin­1 group, the ALP activity of the MC3T3­E1 cells was increased, and the ARS staining area was also increased. The mRNA and protein expression levels of BMP2, Runt­related transcription factor 2, collagen1, osteopontin, osteocalcin and osterix in the omentin­1 group were also significantly upregulated. All these effects were reversed following treatment with SIS3 HCl. These results demonstrated that omentin­1 can significantly promote osteoblast viability and differentiation via the TGF­ß/Smad signaling pathway, thereby promoting bone formation and preventing osteoporosis.

Enhancing the Pharmacokinetic Profile of Interleukin 2 through Site-Specific Conjugation to a Selective Small-Molecule Transthyretin Ligand.

Protein drugs hold great promise as therapeutics for a wide range of diseases. Unfortunately, one of the greatest challenges to be addressed during clinical development of protein therapeutics is their short circulation half-life. Several protein conjugation strategies have been developed for half-life extension. However, these strategies have limitations and there remains room for improvement. Here, we report a novel nature-inspired strategy for enhancing the in vivo half-life of proteins. Our strategy involves conjugating proteins to a hydrophilic small molecule that binds reversibly to the plasma protein, transthyretin. We show here that our strategy is effective in enhancing the pharmacokinetic and pharmacodynamic properties of human interleukin 2 in rats, potentially opening the door for more effective and safer cancer immunotherapies. To our knowledge, this is the first example of successful use of a small-molecule that not only extends the half-life but also maintains the smaller size, binding potency, and hydrophilicity of proteins.

Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents.

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance toward effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.

Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis.

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While pathogenic TTR mutations (TTRm) destabilize TTR tetramers, the T119M variant stabilizes TTRm and prevents disease. A comparison of potency for leading TTR stabilizers in clinic and structural features important for effective TTR stabilization is lacking. Here, we found that molecular interactions reflected in better binding enthalpy may be critical for development of TTR stabilizers with improved potency and selectivity. Our studies provide mechanistic insights into the unique binding mode of the TTR stabilizer, AG10, which could be attributed to mimicking the stabilizing T119M variant. Because of the lack of animal models for ATTR-CM, we developed an in vivo system in dogs which proved appropriate for assessing the pharmacokinetics-pharmacodynamics profile of TTR stabilizers. In addition to stabilizing TTR, we hypothesize that optimizing the binding enthalpy could have implications for designing therapeutic agents for other amyloid diseases.

Structural characterization, antioxidant and hepatoprotective activities of polysaccharides from Sophorae tonkinensis Radix.

In current study we present two polysaccharides, STRP1 and STRP2, purified from Sophorae tonkinensis Radix via column chromatography. Structural analyses indicated that STRP1 and STRP2 were consisted of mannose, rhamnose, glucuronic acid, glucose, galactose and arabinose in a similar molar ratio with main backbones of (1 → 3)-linked-α-d-Gal and (1 → 4)-linked-α-d-Glc, while average molecular weights were 1.30 × 104 and 1.98 × 105 Da, respectively. We observed a strong chelating ability on ferrous ions; substantial radical scavenging activities on DPPH, hydroxyl and superoxide anion radicals in vitro; and significant attenuation on acetaminophen-induced hepatic oxidative damage in mice for STRP1 and STRP2. The promising data on these polysaccharides showcase the need to further develop novel natural antioxidant and liver-protecting drugs.

Cinnamaldehyde prevents endothelial dysfunction induced by high glucose by activating Nrf2.

BACKGROUND/AIMS: It is well documented that hyperglycemia-induced oxidative stress is an important causative factor of endothelial dysfunction. Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can enhance the antioxidant defense against reactive oxygen species (ROS) by activating NF-E2-related factor 2 (Nrf2), which has been shown to have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown. METHODS: Dissected male C57BL/6J mouse aortic rings and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM) DMEM treatment with or without CA (10 µM). RESULTS: Treatment with CA protected the endothelium relaxation, inhibited ROS generation and preserved nitric oxide (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up-regulated Nrf2 expression, promoted its translocation to the nucleus'and increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition. The increased level of nitrotyrosine in HUVECs under high glucose was also attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining indicated that CA inhibited the ROS generation and preserved the NO levels in HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions. CONCLUSION: Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications.

Association between Peroxisome Proliferator-activated Receptor Gamma Gene Polymorphisms and Atherosclerotic Diseases: A Meta-analysis of Case-control Studies.

AIM: The aim of this study was to perform a meta-analysis to investigate the association between PPARγ rs1801282/rs3856806 polymorphisms and atherosclerotic diseases. METHODS: The meta-analysis was performed by searching the PubMed, Embase and Web of Science databases from the first available year to September 10, 2013. Additionally, reference lists from the identified articles, reviews and abstracts presented at the meetings of related scientific societies were also checked. All case-control studies investigating the association between PPARγ rs1801282/rs3856806 polymorphisms and the risk of atherosclerotic disease were included. The association was assessed according to the odds ratio (OR) with a 95% confidence interval (CI). Publication bias was analyzed using Begg's funnel plot and Egger's regression test. RESULTS: A total of 29 studies reporting PPARγ rs1801282/rs3856806 polymorphism were included in the final meta-analysis. Neither the rs1801282 (Pro12Ala) nor rs3856806 (C161T) polymorphisms showed any significant associations with susceptibility to atherosclerotic diseases. In the meta-analysis performed to assess the association between the rs3856806 gene polymorphism and atherosclerotic disease based on ethnicity and the type of disease, significant associations were found in the Caucasian subgroup, Asian, CAD and MI subgroups. CONCLUSIONS: The present data suggest that there is no statistical evidence of a significant association between the PPARγ gene rs1801282/rs3856806 polymorphism and the risk of atherosclerotic disease. In contrast, the rs3856806 polymorphism was associated with an increased risk in the Caucasian and MI subgroups, whereas decreased risks were noted in the Asian and CAD subgroups. Due to significant between-study heterogeneity, further studies with a larger sample size involving homogeneous AS patients and well-matched controls are required in the future.

[Association of MK2 gene polymorphisms with low-density lipoprotein cholesterol and tumor necrosis factor-alpha in Uygur population from Hetian area of Xinjiang].

OBJECTIVE: To investigate the association of MK2 gene with low density lipoprotein cholesterol (LDL-C) and tumor necrosis factor-alpha (TNF-Α) between different gender in Xinjiang Uygur population. METHODS: A total of 350 Uygur males and 595 females were recruited randomly from Hetian area. Two single nucleotide polymorphisms (44890c/t, rs 45514798) in MK2 gene were selected and genotyped by Taqman-PCR in these subjects. All subjects underwent questionnaire-based survey, physical examination, measurement of lipid profiles and plasma TNF-Α determination. RESULTS: Among the male subjects, the concentration of total cholesterol (TC) [TT vs. CT vs. CC: (4.35±1.20) mmol/L vs. (4.69±1.34) mmol/L vs. (4.83±1.44) mmol/L, P=0.033]and TNF-Α [TT vs.CT vs.CC: (106.63±62.39) ng/dL vs. (128.44±86.15) ng/dL vs. (153.06±82.99) ng/dL, P=0.001]were significantly different in 3 genotypes of 44890c/t. However, the LDL-C levels in TT, CT, and CC genotypes of 44890c/t were not different neither in males nor in females [males: (2.64±1.16) mmol/L vs. (2.81±1.28) mmol/L vs. (3.04±1.32) mmol/L, P>0.05; females: (2.42±1.11) mmol/L vs. (2.36±0.99) mmol/L vs. (2.43±1.05) mmol/L, P>0.05]. None of the allele and genotype frequencies of 44890c/tand rs 45514798 were different between high LDL-C group and control group. Linear regression analysis indicated that body mass index (BMI) (beta=0.089) and TNF-Α (beta=0.092) were significantly associated with LDL-C levels in males (P<0.05), while the age, BMI, and waist/hip ratio with LDL-C levels in females (P<0.05). CONCLUSION: The nucleotide polymorphisms (44890c/t and rs 45514798) in MK2 gene may not be associated with LDL-C in both males and females in the Uygur population in Hetian, Xinjiang.

[Epidemiological survey of lipid levels and factors in Kazakan people over 30-year old in Fukang of Xinjiang].

OBJECTIVE: To study the lipids level in Kazakan individuals over 30-year-old in Fukang area of Xinjiang. METHODS: Random cluster multistage sampling method were performed to select the subjects, and 991 individuals aged older than 30 from Fukang of Xinjiang were included. The plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), plasma glucose and insulin were measured. Related adverse cardiovascular risk factors were discussed. RESULTS: The mean plasma TC, TG, HDL-C and LDL-C of Kazakan residents over 30-year-old in Fukang of Xinjiang were (5.05 ± 1.07), (1.10 ± 0.66), (1.46 ± 0.38) and (3.06 ± 0.84) mmol/L, respectively. TC, TG and LDL-C levels in male subjects were higher than those in females (male vs female: TC: (5.19 ± 1.05) mmol/L vs (4.94 ± 1.07) mmol/L, t = 3.57, P < 0.01; TG: (1.32 ± 0.80) mmol/L vs (0.94 ± 0.46) mmol/L, t = 8.63, P < 0.01; LDL-C: (3.30 ± 0.85) mmol/L vs (2.88 ± 0.79) mmol/L, t = 8.06, P < 0.01). While the HDL-C level in male subjects was lower than that of female (male vs female: (1.32 ± 0.33) mmol/L vs (1.57 ± 0.38) mmol/L, t = 11.48, P < 0.01). The prevalence of dyslipidemia was 28.3% (280/991) in the overall populations. In the overall populations, the prevalence of hypercholesteremia, hypertriglyceridemia, high low-density lipoprotein cholesterolemia and low serum high density lipoprotein cholesterolemia were 12.6% (125/991), 6.6% (65/991), 11.0% (109/991) and 10.1% (100/991), respectively. The prevalence of individuals with borderline-high TC, TG and LDL-C were 27.0% (268/991), 7.6% (75/991) and 20.5% (203/991), respectively. The prevalence of dyslipidemia was 40.0% (172/430) in male populations. The prevalence of dyslipidemia in group aged 30 - 39, 40 - 49, 50 - 59, 60 and above were 26.2% (78/298), 26.0% (91/350), 31.2% (73/234) and 34.9% (38/109), respectively, the trend of prevalence was significant by trend test for groups comparison (χ(2) = 3.94, P < 0.05). Adjusting for age and gender, TG was positively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were 0.368 (P < 0.01), 0.336 (P < 0.01) and 0.331 (P < 0.01), respectively, and HDL-C was negatively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were -0.340 (P < 0.01), -0.339 (P < 0.01) and -0.321 (P < 0.01), respectively. CONCLUSION: The lipid levels of Kazakan residents from Fukang area are high and are characterized by hypercholesteremia and high low-density lipoprotein cholesterolemia, and more attention of the prevention of dyslipidemia in this populations should be paid to males, border-line abnormal and those aged over 60-year old.

[Negative association of STAMP2 gene polymorphisms with essential hypertension in Xinjiang Uygur population].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of the six transmembrane protein of prostate 2 gene (STAMP2) and essential hypertension in Xinjiang Uygur population. METHODS: The sequences of STAMP2 gene functional region were sequenced in Xinjiang Uygur population with hypertension. The representative variations selected were genotyped by TaqMan-PCR method in 2047 Uygur individuals, including 810 patients with hypertension and 1237 healthy subjects. The association of the genetic variations of the STAMP2 gene with hypertension in Uygur was analyzed. RESULTS: In the three representative variations (rs8122, rs1981529 and rs34741656) genotyped, there were no significant differences in genotype distribution and allele frequencies between the essential hypertension and control groups (P > 0.05). In ANCOVA analysis, none of the polymorphisms was significantly associated with systolic blood pressure and diastolic blood pressure (P > 0.05). There were no significant differences in haplotype frequencies between the two groups either(P > 0.05). CONCLUSION: There was no association of the three polymorphisms (rs8122, rs1981529 and rs34741656) in the STAMP2 gene with essential hypertension in Xinjiang Uygur population.