Ala Allele Research Articles

Peroxisome Proliferator-Activated Receptor-γ Gene Polymorphism in Psoriasis and Its Relation to Obesity, Metabolic Syndrome, and Narrowband Ultraviolet B Response: A Case-Control Study in Egyptian Patients.

Background:Psoriasis is a common dermatologic disease with multifactorial etiology in which genetic factors play a major role. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in keratinocytes and is known to affect cell maturation and differentiation in addition to its role in inflammation.Aim:To study the association between PPAR-γ gene polymorphism and psoriasis vulgaris in Egyptian patients to explore if this polymorphism influenced disease risk or clinical presentation.Methods:Forty-five patients with psoriasis vulgaris and 45 age, sex and body mass index matched healthy volunteers who have no present, past or family history of psoriasis as a control group were enrolled. Selected cases included obese and nonobese participants. Detection of PPAR-γ gene polymorphism was done with restriction fragment length polymorphism polymerase chain reaction. Narrow-band ultraviolet B (NBUVB) was given for every case three times/week for 12 weeks.Results:Homopolymorphism, heteropolymorphism, and Ala allele were significantly associated with cases (P = 0.01, P = 0.01, and P = 0.004, respectively) and increased risk of occurrence of psoriasis by 5.25, 3.65, and 3.37 folds, respectively. Heteropolymorphism was significantly associated with nonobese cases compared to obese ones (P = 0.01). Ala allele was significantly associated with obese cases (P = 0.001) and increased risk of occurrence of psoriasis in obese participants by 1.14 folds. Homopolymorphism, heteropolymorphism, and Ala allele were more prevalent among obese cases without metabolic syndrome (MS) than obese cases with MS but without statistical significance. Percentage of decrease of mean Psoriasis Area and Severity Index score before and after 3 months of treatment with NBUVB was higher in cases with heteropolymorphism with no significant difference between homo- and heteropolymorphism.Conclusion:PPAR-γ gene polymorphism is associated with and increased the risk of psoriasis and its associated obesity in Egyptian patients. It has no role in NBUVB response in those patients. Future large-scale studies on different populations are recommended.

The Single Nucleotide Polymorphism PPARG2 Pro12Ala Affects Body Mass Index, Fat Mass, and Blood Pressure in Severely Obese Patients.

Background The PPARG2 Pro12Ala (rs1801282) and IL6 -174G >C (rs1800795) have important function in body weight regulation and a potential role in obesity risk. We aimed to investigate the association between PPARG2 Pro12Ala and IL6 -174G >C variants and the genotypes interaction with body composition, metabolic markers, food consumption, and physical activity in severely obese patients. Methods 150 severely obese patients (body mass index (BMI) ≥ 35 kg/m2) from Central Brazil were recruited. Body composition, metabolic parameters, physical activity, and dietary intake were measured. The genotype was determined by the qPCR TaqMan Assays System. Multiple linear regression and multiple logistic regression models were fitted adjusting for confounders. Results Ala carriers of the Pro12Ala polymorphism had higher adiposity measures (BMI: p=0.031, and fat mass: p=0.049) and systolic blood pressure (p=0.026) compared to Pro homozygotes. We found no important associations between the -174G >C polymorphism and obesity phenotypes. When genotypes were combined, individuals with genotypes ProAla + AlaAla and GC + CC presented higher BMI (p=0.029) and higher polyunsaturated fatty acids (PUFAs) consumption (p=0.045) compared to the ones with genotypes ProPro and GG, and individuals carriers of the PPARG2 Ala allele only (genotype ProAla + AlaAla and GG) had higher fat mass and systolic and diastolic blood pressure compared to the ones with genotypes ProPro and GG. Conclusions Severely obese individuals carrying the Ala allele of the PPARG2 Pro12Ala polymorphism had higher measures of adiposity and blood pressure, while no important associations were found for the IL6 -174G >C polymorphism.

The Association between the Alpha-Fibrinogen Thr312Ala (rs6050) Polymorphism and Risk of Venous Thromboembolism Among Enrollees in the Gate Study

Introduction: The final events of the activated clotting cascade include the conversion of fibrinogen to fibrin and stabilization of the growing fibrin clot by factor XIII (FXIII). A missense variant in the alpha chain of fibrinogen, α-fibrinogen (FGA) Thr312Ala (rs6050, NM_000508.3:c.991A>G, NP_000499.1:p.[Thr331Ala]), has been previously shown to interfere with FXIII-dependent cross-linking, leading to stiffer blood clots. It is believed this pathophysiology underlies the increased risk of venous thromboembolism (VTE) associated with the variant. The Thr312Ala variant has been shown to be significantly associated with VTE among White, Non-Hispanic populations. The only investigation of the variant in a Black population (Rasmussen-Torvik et al 2007) found no significant relationship between Thr312Ala and VTE, but the authors cite the relatively small number of participants included in the analysis as a possible reason for a null finding. We investigated the association between FGA Thr312Ala and VTE in a case-control study enrolling a relatively large racially diverse study population.Methods: Conditional logistic regression was used to assess the association between FGA Thr312Ala and VTE among enrollees in the Genetic Attributes and Thrombosis Epidemiology (GATE) study, a case-control study enrolling 1,042 VTE cases and 1,213 controls with no history of VTE, frequency-matched on age, sex, and race. Crude models conditioned on the matching factors, and adjusted models conditioned on the matching factors and controlled for patient characteristics found to be associated with both case/control status and FGA Thr312Ala genotype. Among all patient characteristics evaluated, the β-fibrinogen (FGB) promoter region variant -455 G>A (rs1800790, NM_001184741.1:c.-463G>A) was the only patient characteristic associated with both case/control status and FGA Thr312Ala genotype. Potential effect modification was assessed using likelihood ratio tests.Results: Among 660 White controls and 528 White cases in the GATE study, carrying at least one FGA rs6050 G (Ala) allele was associated with increased odds of VTE compared to not carrying a G allele (odds ratio (OR) and 95% confidence interval (CI) 1.2 [1.0-1.5]) in a crude model. This association was strongest when restricting to n=205 idiopathic (unprovoked) cases, n=125 recurrent cases, or n=112 cases exhibiting both deep vein thrombosis (DVT) and pulmonary embolism (PE) (Table 1). This association was modified by obesity status, with the effect among obese enrollees being multiplicative (Table 2). In contrast, there was no association between carrying at least one FGA rs6050 G (Ala) allele and VTE among 553 Black controls and 514 Black cases in the GATE study (OR and 95% CI 1.0 [0.8-1.2]) when assessing the association among all cases (Table 1). However, the odds of VTE was higher among Black participants carrying the G allele compared to those not carrying the allele when restricting to n=103 PE only cases (OR and 95% CI 1.5 [1.0-2.4]). The association between FGA Thr312Ala and VTE did not appear to be modified by obesity status among Black participants (Table 2).Conclusions: These results indicate that the FGA Thr312Ala (rs6050, NM_000508.3:c.991A>G, NP_000499.1:p.[Thr331Ala]) polymorphism is associated with VTE among White participants in the GATE study, with the strongest effect seen in participants exhibiting both DVT and PE. However, the association among Black participants appears limited to PE, indicating further exploration of genetic risk factors for VTE in Black populations is warranted in order to better understand genetic risk factors for all types of VTE in this population. [Display omitted] DisclosuresPayne:Bayer: Other: treatment product donation; Bioverativ: Other: treatment product donation; Novo Nordisk: Other: treatment product donation; Shire: Other: treatment product donation; Genentech: Membership on an entity's Board of Directors or advisory committees. Patel:Daiichi Sankyo: Other: DSMB member.

Association between PPARs Gene Functional Polymorphisms and Ischemic Stroke in Chinese Uyghur Population.

PPARγ and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). We recruited 100 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 100 normal healthy controls from Chinese Uyghur Population to assess the nature of the functional polymorphisms of PPARs and any links with IS in this unique population which has 60% European ancestry and 40% East Asian ancestry. We found that the Ala allele of the PPARγ Pro12Ala polymorphism was more common in controls than IS subjects (P = 0.008, corrected for multiple testing) in the Uyghur Population. Pro/Ala carriage may be associated with a decreased risk of IS in Uyghurs (OR 0.542, 95% CI 0.346-0.850). Additionally, the 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Uguhur IS patients and controls. Our population and ethnic-based study demonstrates that the 162Val allele frequency was extremely low in the Chinese Uyghur Population different from Some European and African populations and the PPARγ 12 Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Uyghur Population.

Thr83ala Gene Polymorphism Association with Arterial Calcification, Acute Coronary Syndrome and Ischemic Strokes in Older Adults.

BACKGROUND:Calcification of the arteries of the lower extremities is a very common pathological process, which has an independent significance in the development of cardiovascular diseases. There is evidence that development of calcification of the arteries correlates with a mutation of the MGP protein gene representing by the Thr83Ala polymorphism.AIM:The purpose of the study was to analyse the connection of Thr83Ala polymorphism of the MGP gene with the development of calcification of the arteries of the lower extremities.METHODS:The study involved 80 patients. Half of them had signs of calcification of the arteries of the lower extremities. The allelic Thr83Ala polymorphism of the MGP protein gene was determined by polymerase chain reaction, establishing the presence of calcification of the arteries by radiological and dopplerographic methods.RESULTS:The study aimed to analyse the association of the Thr83Ala polymorphism of the matrix Gla protein gene with the development of calcification of the arteries of the lower extremities. The data obtained suggest that the replacement of threonine by alanine in the 83rd position of the MGP molecule can affect the functional properties of the protein and in particular its anticarcinogenic properties. Although there was no difference in the distribution of different variants of the genotype by Thr83Ala to the MGP gene polymorphism in patients with CA and healthy patients, but in the distribution of genotypes in the comparison groups separated by sex, it was found that in women, carriage of the Ala allele in a homozygous state is a factor, which protects the development of arterial calcination in the elderly and senile.CONCLUSION:Differences in the distribution of different variants of the genotype according to Thr83Ala to the polymorphism of the MGP gene between patients with CAD and healthy patients do not exceed the limits of statistical significance. In the distribution of genotypes in the comparison groups divided by sex, it was found that in women the carrier of the Ala-allele in the homozygous state is a factor that prevents the development of Menkeberg arteriosclerosis in the elderly and old age.

Role of peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism in human adipose tissue: assessment of adipogenesis and adipocyte glucose and lipid turnover

ABSTRACTThe protective mechanisms of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala polymorphism in type 2 diabetes (T2D) are unclear. We obtained subcutaneous adipose tissue (AT) before and 3 h after oral glucose (OGTT) in carriers and non-carriers of the Ala allele (12 Pro/Pro, 15 Pro/Ala, and 13 Ala/Ala). Adipogenesis, adipocyte glucose uptake and lipolysis as well as PPARγ target gene expression were investigated and compared between the genotype groups. During fasting and post-OGTT, neither basal nor insulin-stimulated adipocyte glucose uptake differed between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro (p < 0.05) was accompanied with a higher antilipolytic effect of insulin post-OGTT (p < 0.01). The adipocyte size was similar across groups. Preadipocyte differentiation rates between Pro/Pro and Ala/Ala were unchanged. In conclusion, no major differences in AT differentiation, glucose uptake, lipolysis or expression of PPARγ target genes were observed between different PPARγ Pro12Ala genotypes. Albeit small, our study may suggest that other pathways in AT or effects exerted in other tissues might contribute to the Pro12Ala-mediated protection against T2D.

PPARG2 Pro12Ala polymorphism influences body composition changes in severely obese patients consuming extra virgin olive oil: a randomized clinical trial

BackgroundPrevious intervention studies have reported the association of the PPARG2 Pro12Ala (rs1801282) and IL6 -174G > C (rs1800795) polymorphisms with weight loss; however, their results are inconsistent. We aimed to investigate the effect of the PPARG2 Pro12Ala and IL6 -174G > C polymorphisms on body weight, body composition and metabolic parameters after a 12-week nutritional intervention with a traditional Brazilian diet and extra virgin olive oil supplementation in severely obese patients.MethodsA total of 149 severely obese individuals [body mass index (BMI) ≥ 35 kg/m2] were randomized into three 12-week nutritional intervention groups – the extra virgin olive oil supplementation (OO) group (n = 50), the traditional Brazilian diet (DieTBra) group (n = 49), and the DieTBra plus extra virgin olive oil supplementation (DieTBra+OO) group (n = 50). Anthropometric measurements, body composition, metabolic parameters, physical activity practise and dietary intake were assessed. The associations were tested using generalized linear models adjusted for confounders.ResultsThe PPARG2 Pro12Ala polymorphism influenced body composition changes. Ala carriers in the intervention groups with extra virgin olive oil supplementation had greater reductions in the percentage of body fat (%BF) (OO: p = 0.049, DietBra+OO: p = 0.004) and greater increases in both fat-free mass (FFM) (OO: p = 0.020, DieTBra: p = 0.007) and lean mass (LM) (OO: p = 0.020, DieTBra+OO: p = 0.007) than did ProPro homozygotes. No association was found for the IL6 -174G > C polymorphism.ConclusionsExtra virgin olive oil intake may modulate favourable body composition changes, promoting a decrease in the %BF and increases in the LM and FFM of severely obese individuals, even without weight loss, in the presence of the Ala allele of the Pro12Ala polymorphism.Trial registrationRegistered under ClinicalTrials.gov Identifier No. NCT02463435.

The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study

BackgroundSeveral studies have shown significant associations between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and diabetic complications, but this association has not been explored in relation with chronic kidney disease (CKD) in Type 2 diabetes mellitus (T2DM) patients. Total antioxidant capacity (TAC) level changes in diabetic condition and may play important role in onset or progression of the disease and its complications. The present study investigated the association of MnSOD Val16Ala polymorphism and serum TAC with the risk of CKD in T2DM patients.MethodsThis nested case-control study included 280 type 2 diabetic patients with CKD and 280 age, sex and diabetes duration-matched control subjects selected from the participants of the Tehran Lipid and Glucose Study. MnSOD val16Ala (rs4880) SNP was genotyped by the Tetra-Primer ARMS-polymerase chain reaction analysis. Serum TAC was measured using ferric-reducing antioxidant power assay. Statistical analysis was performed using STATA statistical package v.12.0 or SPSS (Version 22.0).ResultsThe Ala allele of the MnSOD Val16Ala polymorphism was associated with a lower risk of CKD (odds ratio (OR), 0.55; 95% confidence interval (CI), 0.36–0.84; P = 0.006). Median serum TAC in CKD group was 920 μmol/L and was significantly lower (p < 0.001) compared to the control group (1045 μmol/L). Using an adjusted conditional logistic regression, we didn’t observe any significant interaction between MnSOD Val16Ala SNP with quartiles of serum TAC in relation to CKD.ConclusionA significant association was found between the MnSOD Val16Ala polymorphism and CKD, but this association is not affected by serum TAC level in T2DM patients.

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.

Is the rs1801282 (G/C) Polymorphism of PPAR - Gamma Gene Associated with T2DM in Iraqi People?

BACKGROUND:Pro12Ala (rs1801282) is a common polymorphism of the human PPAR-γ gene. Studies have demonstrated conflicting results about its association with T2DM worldwide. There are no reports about such possible association among Iraqi people.OBJECTIVES:This study aims at finding out whether having the mutant allele (Ala12) might be associated with T2DM among Iraqi people.METHODS:One hundred and ninety-two Arabic Iraqi adult subjects (97 with T2DM and 95 controls) were genotyped using PCR- RFLP. Clinical, anthropometrical and biochemical variables were compared regarding the Pro12Ala genotypes.RESULTS:About 5.67% of people with diabetes were carriers of the (Ala12) allele versus 9.47% of controls. Allelic and genotypic frequencies were not statistically different among diabetics and controls [(χ2= 1.99, p= 0.16) and (χ2= 2.17, p= 0.14)]. Age, BMI and smoking- but not Pro12Ala - were independent risk factors for T2DM in our subjects. Pro12Ala was not associated with T2DM (Odd’s ratio 0.55, 95% CI 0.23- 1.32, p= 0.14).CONCLUSIONS:Our study revealed a relatively high frequency of the Ala12 allele among Arabic Iraqis. These frequencies did not significantly differ between diabetics and controls indicating the absence of association of Pro12Ala with T2DM among Iraqis.

Lipid Metabolism Regulate the Inflammatory Microenvironment in the Hepatic Fibrosis Induced by Schistosoma Japonicum Infection in China: A Genotype-Phenotype Association Study

Background: Schistosomiasis (japonica) is a neglected infectious disease, influencing millions of people at risk of infection worldwide. The patients are at high risk of gradually developing hepatic fibrosis. Immune regulation is recognized to contribute to schistosomal liver fibrosis. However, we still lack appropriate preventive and therapeutic modalities. Previous evidence points out that there is an interaction between lipid regulation and inflammation which moderates the homeostasis after parasitic infection. Moreover, while immune response to Schistosoma infection is considered affected by genetic diversity; yet so far little is known regarding the mechanism of action. To explore the association between lipid metabolism-related genes and the hepatic fibrosis induced by Schistosoma japonicum infection, we conducted the following study. Methods: This study combines epidemiological investigation, in-vitro studies, and animal experiment. First, we conducted a whole-genome sequencing in the epidemic area of China and established a S. japonicum-infected mice model and liver tissue morphology and mRNA analysis of PLA2G2D and PPARG were conducted. Then we expanded the sample size and collected biological information under epidemiological investigation. This was followed with genotyping of the candidate genes, the serum protein expression, as well as the level of three inflammation-related lipid mediators, which were measured and compared in different groups. Finally, we evaluated whether the allelic changes alter PLA2G2D enzymatic activity in vitro and compared the Pro and Ala PPARγ forms concerning the ability to activate transcription via dimerizing with the retinoid X receptor α (RXRα) and response element (PPRE). Findings: A group of lipid metabolism-related genes in schistosomiasis patients were identified. We found schistosome immunoregulation accompanied by the development of lipid metabolism in the murine model. We confirmed the genetic variation of arachidonic acid metabolic pathway related genes (PLA2G2D rs584367 and PPARG rs1801282) associated with a reduced risk of high grades of schistosomiasis induced hepatic fibrosis in a large sample size. Moreover, the levels of serum PLA2G2D and the 15d-PGJ2、PGE2 and TXB2 showed significant differences due to grades of fibrosis. Besides, the level of TXB2 significantly correlated with PLA2G2D. The enzyme activity of the PLA2G2D was increased approximately four-fold in the variant relative to the wild-type. The PPARγ 12Ala allele showed 18.7%-fold reduction in the ability to transactivate responsive promoters. Interpretation: This study raises a novel perspective conclusion from whole-genome sequencing that lipid metabolism particularly arachidonic acid metabolic pathway may play a regulatory role in the balance of inflammatory microenvironment which is essential for the development of Schistosoma liver fibrosis. Patients with risk polymorphism have more probability to develop uncontrollable inflammation, which eventually progress to hepatic fibrosis. The significant markers we found in this investigation may be used to facilitate diagnosis. Funding Statement: This study was supported by National Natural Science Foundation of China (Grant Number: 81601781) and the China Postdoctoral Science Foundation (Grant Number: 2016M591605), Science and Technology Program of Guangzhou (Grant Number: 201803010116). Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: Epidemiological studies were approved by the Ethics Committees of Fudan University (IRB#2016-TYSQ-03-17), and all participants gave informed written consent. Animals were cared for by the guidelines developed by the China Council on Animal care, and all animal experiments were performed according to the procedures approved by the Human Research Ethics Committee of the Sun Yat-sen University (No·2016-104).

ASSOCIATION OF THE HUMAN PPARγ2 PRO12ALA POLYMORPHISM WITH OBESITY IN A POPULATION FROM TURKEY.

There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the gender-stratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

Molecular-genetic risk factors of non-alcoholic fatty liver disease and obesity in patients with arterial hypertension

The objective: to analyze the role of polymorphic variants of the Peroxisome Proliferator-Activated Receptor-γ2 (PPAR-γ2, Pro12Ala) and angiotensin converting enzyme (ACE, I/D) genes as possible causative risk factors of Non-alcoholic Fatty Liver Disease (NAFLD), Abdominal Obesity (AO), Diabetes Mellitus type 2 (DM 2) in essential arterial hypertension (EAH) patients.Materials and methods. 96 patients with non-alcoholic fatty liver disease (NAFLD), EAH II stage, of 1–2 degrees of blood pressure, high and very high risk with concomitant AO participated in the research: 41,67% (40) men and 58,33% (56) women, the average age was 53,70±5,34 years. The function of the liver was studied by the activity of organ specific enzymes. The polymorphism of PPAR-γ2 (Pro12Ala) and АСЕ (I/D) genes were studied by the PCR based method. The control group included 50 practically healthy subjects.Results. Among the residents of the Northern Bukovyna suffering from NAFLD, AO and EAH the deletion in the 16th intron of the АСЕ (rs 4646994) gene in the homozygous condition occurs in 32,29% of cases, which is by 14.29% more frequently than in the control group sunbjects (χ2=3,38; р=0,048). The DD genotype presence of the АСЕ gene almost double increases the relative risk of NAFLD in general [OR=2,17; р=0,048] and non-alcoholic liver steatosis in particular [OR=2,32; р=0,038], as well as CD2 type [OR=3,46; p=0,015].The PPAR-γ2 (rs1801282) gene genotypes distribution between patients with NAFLD and control group subjects didn’t significantly differ with the prevalence of Pro alleles 3,85 and 6,14 times (p<0.001). The minor Ala-allele presence of the PPAR-γ2 gene (rs1801282) in the genotype increases the relative risk of non-alcoholic steatohepatitis 1.73 times [OR=2,67; p=0,054], however, plays a protective role in the severe obesity degrees appearance [OR=0,29; p=0,008]. The homozygous Pro allele carrier, on the contrary, increases the likelihood of AO ІІ and ІІІ degrees more than 3 times [OR=3,41; p=0,016].Conclusion. The presence of DD genotype of the ACE (rs4646994) gene in patients with EAH is a risk factor of NAFLD in general and non alcoholic liver steatosis in particular, as well as DM 2. The presence of the minor Ala allele of PPAR-γ2 gene (rs1801282) increases the relative risk of non alcoholic steatohep atitis, and the ProPro genotype increases the chances for AO II and III degree appearance.

SOD2 gene polymorphism may modulate biochemical responses to a 12-week swimming training

The aim of the study was to analyze the effect of SOD2 Val16Ala polymorphism on blood biochemical response to chronic swimming training. Healthy men (students of physical education) participated in a swimming training program (ST group) or served as a control group (CON group). The swimming training program lasted 12 weeks (1.5h per day; 4 days per week). Fasting blood samples were obtained prior to (pre) and after (post) a 12-week study period, to measure the biomarkers of oxidative stress, muscle damage and lipid profile. No significant changes in the study parameters were documented in CON group after a 12-week study period, either overall or among carriers of specific SOD2 Val16Ala genotypes. In ST group, post-training decrease in serum lipid hydroperoxides (p < 0.05) and creatine kinase activity (p < 0.05) was associated with Ala/Ala genotype of SOD2 Val16Ala polymorphism. In turn, the increase in serum activity of superoxide dismutase (p < 0.05) was associated with Val carriers, and Val/Val genotype additionally predisposed to the post-training increase in total glutathione level in whole blood (p < 0.05). Moreover, in ST group, a 12-week swimming training program induced an increase in serum concentration of total cholesterol (p < 0.05), which resulted from an increase in both high density (p < 0.05) and low density lipoprotein cholesterol (p < 0.05). The change in high density lipoprotein cholesterol level was irrespective of the genotype. Also, a tendency to post-training increase in both total and low density lipoprotein cholesterol was observed in all three genotypes, although these changes were significant solely in Ala/Val genotype carriers (p < 0.05). In conclusion, 12-week swimming training induces changes in oxidative stress and muscle damage parameters, as well as in lipid profile. These changes seem to be associated with the presence of SOD2 Val16Ala polymorphism. Presence of Ala allele, especially as homozygote, is associated with some beneficial post-training changes, such as a decrease in lipid peroxidation and less pronounced muscle damage. In turn, the influence of SOD2 Val16Ala polymorphism on the changes in lipid profile in response to chronic swimming training should be verified in further study.

Quantitative evaluation of PPAR-γ2 Pro12Ala polymorphism with hypertension.

The peroxisome proliferator-activated receptor γ2 (PPARγ2)Pro12Ala polymorphism has been reported to be associated with hypertension. However, relevant studies have shown inconsistent results. To quantitatively evaluate the relationship between the PPARγ2Pro12Ala polymorphism and hypertension risk, we conducted ameta-analysis based on all available studies selected from Scopus, Web of Science, PubMed, Chinese National Knowledge Infrastructure, and Wanfang databases. In all, 13 studies were finally included in this meta-analysis. In the allelic model (Ala vs. Pro), the Ala allele of PPARγ2 Pro12Ala polymorphism was associated with hypertension (Odds Ratio [OR]= 0.723, 95% confidence interval [CI]= 0.607-0.861). Sensitivity analysis and exclusion of studies with poor quality scores or controls complicated by other diseases confirmed the validity of this association. Moreover, the PPARγ2Pro12Ala polymorphism was associated with hypertension in the codominant (OR= 0.710, 95% CI= 0.626-0.806), recessive (OR= 0.561, 95% CI= 0.418-0.754), and dominant (OR= 0.693, 95% CI= 0.577-0.833) models. The Ala allele appears to have aprotective effect against hypertension and adominant function.

Associations between PPARG polymorphisms and the risk of essential hypertension.

BackgroundPeroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the pathogenesis and maintenance of essential hypertension (EH). It has been suggested that polymorphisms of PPARG are associated with the risk of EH. However, findings to date remain controversial. To elucidate the associations between the PPARG Pro12Ala and C161T polymorphisms and EH risk, a meta-analysis was carried out.MethodsA comprehensive literature search of PubMed, Embase, CNKI (Chinese National Knowledge Infrastructure), VIP and Wanfang databases was conducted. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated to estimate the size of the effect using the random-effects model. At the same time, the pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of the PPARG Pro12Ala polymorphism and blood pressure.ResultsFinally, Fifteen papers (seventeen studies) including 4,151 cases and 4,997 controls to evaluate the association of the PPARGPro12Ala polymorphism and EH risk, were included in this study. Overall, the results suggested that Ala allele was associated with the decreased EH risk (for allelic model, OR = 0.757, 95%CI: 0.624–0.918, P = 0.005; for dominant model, OR = 0.771, 95%CI: 0.627–0.946, P = 0.013). The subgroup analysis stratified by ethnicity showed that the significant association between the PPARG Pro12Ala polymorphism and EH was only detected in the Asian subgroup. There was no difference in blood pressure values between Ala carriers and non-carriers. For the C161T polymorphism, only 5 studies comprising 1,118 cases and 1,357 controls met the inclusion criteria. The overall results showed that the PPARG C161T polymorphism was not associated with the risk of EH. But in the subgroup analysis, we found that the PPARG C161T polymorphism significantly associated with the risk of EH in the Asian subgroup (for allelic model, OR = 0.719, 95% CI: 0.537–0.963, P = 0.027; for dominant model, OR = 0.653, 95% CI: 0.439–0.972, P = 0.036).ConclusionOur meta-analysis suggested that the PPARG polymorphisms might be associated with the risk of EH.

Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors

BackgroundCardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG − rs1801282 − Pro12Ala) and in apolipoprotein E gene (APOE − rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors.MethodsThis was a cross-sectional study with 115 adolescents aged 10–19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student’s t test or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile.ResultsAdolescents carrying PPARG Ala allele showed higher serum triglycerides (p = 0.0423) and very low-density lipoprotein (p = 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p = 0.0712) and very low-density lipoprotein (p = 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele.ConclusionThe polymorphisms PPARG rs1801282 and APOE rs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.

Influence of AHRR Pro189Ala polymorphism on kidney functions.

The function of aryl hydrocarbon receptor repressor (AHRR) in the kidney is unclear. The present study investigated associations between AHRR Pro189Ala polymorphism and estimated glomerular filtration rates (eGFR), serum creatinine, and hemoglobin levels in 2775 Japanese adults without diabetes. In addition, we examined whether AHRR expression levels in the kidney of control and chronic kidney disease (CKD) rats were changed. Multiple linear regression analyses showed that carriers of the Ala allele had increased eGFR and lower concentrations of serum creatinine and hemoglobin (p<0.05). Immunohistochemical analysis showed that the expression of AHRR was upregulated in the kidneys of rats with CKD. These findings suggest that AHRR plays distinct roles in kidney functions and hemoglobin values. The effects of the AHRR polymorphism might be intensified in the kidneys of patients with CKD.

Relationship between renal function and periodontal disease in community-dwelling elderly women with different genotypes.

The aim of this study was to examine the association between periodontal disease and renal function in elderly women with different genotypes. A total of 332 postmenopausal never-smoking women were analysed. Poor renal function was defined as serum cystatin C>0.91mg/l. Periodontal disease markers such as periodontal inflamed surface area (PISA) were evaluated. Selected variables, including PISA quartile, body mass index (BMI), HbA1C and age in Arg allele carriers and non-carriers based on the beta-3 adrenergic receptor, or between Ala allele carriers and non-carriers based on peroxisome proliferator-activated receptor gamma, were analysed using multiple logistic regression analysis. The odds ratios of serum cystatin C level and PISA (fourth quartile) were significantly positive for both Arg (2.52; p=0.035) and Ala allele non-carriers (2.36; p=0.021). A significant association was also found between serum cystatin C level and BMI for both Arg (1.18; p=0.001) and Ala allele non-carriers (1.12; p=0.003). The results of this study suggest that periodontal inflammation might be associated with renal function. Furthermore, in both the Arg and Ala allele non-carriers, the associations between BMI and PISA for renal function became stronger.

Oxidative stress gene polymorphisms may have an impact in the development of ischemic stroke.

Antioxidants are responsible for detoxification of harmful effects of reactive oxygen species. Genetic factors may influence antioxidant activity as a result of polymorphisms on antioxidant enzymes. These polymorphisms can be risk in ischemic stroke (IS) risk. IS is a disorder with genetic and environmental factors contributing to overall risk. Although a few studies have been conducted, there have been no reports on catalase (CAT C262T), manganese superoxide dismutase (MnSOD Ala16Val) and glutathione peroxidase 1 (GPX1 Pro198Leu) gene polymorphisms and IS risk. We aimed to perform a case-control study to increase the awareness of the impact of oxidative stress (OS) gene polymorphism in the development of IS. A restriction fragment length polymorphism-polymerase chain reaction was used to determine genotypes. The interactions between genes and smoking and possible risk factors were evaluated. An approximately four-fold higher IS risk was found in patients with the Val allele compared to the Ala allele. Smoking was a risk factor in the development of IS for CAT TT and MnSOD Ala/Val genotypes; we found a 3.5- to 5.5-fold higher IS risk in CAT TT and MnSOD Ala/Val genotypes. Different logistic regression models were performed for possible risk factors (smoking, body mass index, low-density lipoprotein and diabetes mellitus). The IS risk increases statistically significant only with age by multiple logistic regression analysis. CAT gene polymorphisms in IS patients were not different from controls. It is unlikely that CAT and GPX1 single nucleotide polymorphisms are risk factors for IS. The results of the present study show that smoking may be a risk factor for IS risk in patients with MnSOD mutant genotypes.