Variation in the uncoupling protein 2 and 3 genes and human performance

Uncoupling proteins 2 and 3 (UCP2 and UCP3) may negatively regulate mitochondrial ATP synthesis and, through this, influence human physical performance. However, human data relating to both these issues remain sparse. Examining the association of common variants in the UCP3/2 locus with performance phenotypes offers one means of investigation. The efficiency of skeletal muscle contraction, delta efficiency (DE), was assessed by cycle ergometry in 85 young, healthy, sedentary adults both before and after a period of endurance training. Of these, 58 were successfully genotyped for the UCP3-55C>T (rs1800849) and 61 for the UCP2-866G>A (rs659366) variant. At baseline, UCP genotype was unrelated to any physical characteristic, including DE. However, the UCP2-866G>A variant was independently and strongly associated with the DE response to physical training, with UCP2-866A allele carriers exhibiting a greater increase in DE with training (absolute change in DE of -0.2 ± 3.6% vs. 1.7 ± 2.8% vs. 2.3 ± 3.7% for GG vs. GA vs. AA, respectively; P = 0.02 for A allele carriers vs. GG homozygotes). In multivariate analysis, there was a significant interaction between UCP2-866G>A and UCP3-55C>T genotypes in determining changes in DE (adjusted R(2) = 0.137; P value for interaction = 0.003), which was independent of the effect of either single polymorphism or baseline characteristics. In conclusion, common genetic variation at the UCP3/2 gene locus is associated with training-related improvements in DE, an index of skeletal muscle performance. Such effects may be mediated through differences in the coupling of mitochondrial energy transduction in human skeletal muscle, but further mechanistic studies are required to delineate this potential role.     

解偶联蛋白基因-3826多态性与其mRNA表达相关性的研究

为了探讨解偶联蛋白（ＵＣＰ）基因－３８２６多态性与ＵＣＰｍＲＮＡ表达水平之间可能存在的联系,应用ＲＴ－ＰＣＲ方法测定了ＵＣＰ基因－３８２６多态性野生型（ＡＡ）,杂合子（ＡＧ）和突变纯合子（ＧＧ）３组人群脂肪组织中ＵＣＰｍＲＮＡ的表达水平．定量结果指出：３种基因型（ＡＡ、ＡＧ和ＧＧ）携带者腹膜内脂肪的ＵＣＰｍＲＮＡ表达水平存在极显著差异（Ｐ＜０．０１）,并显示突变等位基因（Ｇ）的数量与ＵＣＰｍＲＮＡ表达水平呈负相关．此结果表明ＵＣＰ基因Ａ→Ｇ（－３８２６）变异与ＵＣＰｍＲＮＡ表达水平降低密切相关．但该变异导致ＵＣＰｍＲＮＡ表达水平降低的机制还有待进一步研究     

绝经后女性CYP19基因Val80及OPG基因A163G多态性与骨密度的相关性研究

探讨细胞色素P450 19 (CYP19) 基因Val80多态性及护骨素(OPG) 基因A163G多态性与绝经后女性骨密度 (BMD) 的关系。随机选择居住在重庆的绝经后女性200例, 采用多聚酶链反应-限制性片段长度多态性法检测Val80及A163G多态性, 采用Norland公司XR-46系列双能X线骨密度仪测量股骨近端及腰椎BMD。 200名绝经后女性中Val80基因型GG、GA及AA的频率分别为19.5％、44.5％及36.0％; A163G基因型GG、GC 及CC的频率分别为: 13.0％, 42.0％及45.0％; 基因型频率分布均符合Hardy-Weinberg平衡 (P＞0.05)。协方差分析及多元逐步回归分析显示CYP19基因第3外显子Val80多态性与绝经后女性BMD无相关性 (P＞0.05)。除大转子外, A163G位点AG/GG/AG+GG基因型者股骨颈、Ward’s三角及腰椎BMD均较AA基因型者低, A163G基因型与股骨颈、Ward’s三角及腰椎BMD有相关性 (P＜0.05)。OPG基因启动子区A163G多态性分布存在明显的种族差异, 且与绝经后女性BMD有一定关联, AA型对BMD具有一定的保护作用, G等位基因是BMD降低的危险因素。     

Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with unfavourable outcomes in patients with acute coronary syndrome

We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10 G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we determined that patients with CAD diagnose and A alleles gene IL10 had unfavorable outcome more often than patients with homozygous G alleles. Survival time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p = 0.042). The group studied do not differ significantly with respect to the distributions of gene IL6 G(-174)C alleles and genotypes. However in case combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C polymorphism we determined that patients with CAD diagnose and carrier genotype GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23, p = 0.017. The obtained data allows assuming the important role of the IL6 and IL10 genes which are responsible for functioning of inflammation system, in the accelerated formation of failures at the patients who had a coronary syndrome.     

Human SMAD4 is phosphorylated at Thr9 and Ser138 by interacting with NLK

A polymorphism in the promoter region of uncoupling protein 2 gene ?866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case–control study. Hormone and glucose levels were estimated using standard protocols. Genotyping of UCP-2 gene polymorphism for all subjects was performed by the PCR–RFLP polymerase chain reaction (PCR) method. Higher Systolic blood pressure, Diastolic blood pressure, Waist to hip ratio, Leptin, Insulin, and blood glucose levels were observed in obese than non-obese (P < 0.05). The distributions of genotype (0.001) and allele (0.003) were significantly different between the non-obese and the obese groups. In the obese group, subjects with the A allele showed significant high insulin levels (<0.001) in comparison with A allele non-carriers. In conclusion, our results suggest that the ?866 AA genotype and A allele of the UCP2 gene is associated with obesity and A allele associated with hyperinsulinemia in obese subjects.     

Effects of UCP2 and UCP3 Variants on the Manifestation of Overweight in Korean Children

To investigate the associations of uncoupling protein (UCP)2 and UCP3 gene variants with overweight and related traits, we genotyped UCP2−866G>A, UCP2Ala55Val, and UCP3−55C>T in 737 Korean children and 732 adults and collected data regarding anthropometric status and blood biochemistry. Information concerning the children's lifestyles and dietary habits was collected. The UCP2−866G>A and UCP3−55C>T gene variants showed significant associations with BMI level, waist circumference, and body weight in the children but not in the adults. Compared with −866GG carriers, the −866GA and AA carriers showed a strong decreasing trend in the risk for overweight (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.45–1.01; P = 0.053). In comparison with UCP3−55CC carriers, children carrying −55CT and TT showed a significant reduction in the risk of overweight (OR, 0.67; 95% CI, 0.46–0.98; P = 0.039). There was also evidence of interactions between the effects of the combined UCP2−UCP3 genotype and obesity‐related metabolic traits. The greatest protective effect against overweight was seen in those with the combined genotype non‐UCP2−866GG and non‐UCP3−55CC, as compared with those carrying both UCP2−866GG and UCP3−55CC (OR, 0.60; 95% CI, 0.38–0.95; P = 0.030). In the subgroup with a low level of physical activity, UCP3−55CC carriers had higher BMI values than UCP3−55T carriers (16.6 ± 2.3 kg/m² vs. 16.1 ± 1.9 kg/m², P = 0.016). Low physical activity may aggravate the susceptibility to overweight in UCP2−866GG and UCP3−55CC carriers.     

Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population

The Adiponectin (ADIPOQ) gene encodes adipose tissue-secreted hormone, Adiponectin, which is secreted to the bloodstream by adipocytes. Adiponectin is a hormone with anti-inflammatory and anti-atherogenic properties and plays a significant role in insulin sensitivity and obesity. The genetic variations in ADIPOQ gene change the circulating adiponectin level and may cause insulin resistance. The aim of the present study is to evaluate the frequency of a common single nucleotide polymorphism (SNP) of ADIPOQ gene (+45T/G) and adiponectin receptor-2 (ADIPOR2) gene (+795G/A) in Iranian population and to correlate these data with other populations. A hundred healthy volunteers were enrolled to identify the genotype of ADIPOQ gene (+45T/G) and ADIPOR2 gene (+795G/A). This was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies for ADIPOQ (+45T/G) were 0.789 for TT, 0.164 for TG, and 0.0468 for GG. Allelic frequencies were 0.87 and 0.13 for T and G, respectively. Genotype frequencies for ADIPOR2 (+795G/A) were 0.09 for AA, 0.3 for AG, and 0.61 for GG; allelic frequencies were 0.24 for A and 0.76 for G. Comparisons between ADIPOQ and ADIPOR2 polymorphisms in Iranian population with those in other populations showed significant differences.     

Association of the muscle-specific creatine kinase (CKMM) gene polymorphism with physical performance of athletes

The aim of the study was to investigate allele and genotype distributions of the muscle-specific creatine kinase gene (CKMM) A/G polymorphism in athletes (n = 384) and controls (n = 1116), and to find interrelation between genotypes and aerobic capacity in rowers (n = 85). Genotyping was performed by restriction fragment length polymorphism analysis. Aerobic capacity (maximal oxygen consumption (VO2(max)) and maximal power production capacity (W(max was determined using an incremental test to exhaustion by rower ergometer. The frequencies of CKMM A allele and AA genotype were significantly higher in endurance-oriented athletes (n = 176) than in controls (A allele: 78.7% vs. 65.4%; p < 0.0001; AA genotype: 59.7% vs. 44.2%; p = 0.0003). On the other hand, GG genotype was more prevalent in weightlifters (n = 74) in comparison with controls (31.1% vs. 13.4%; p = 0.0001). Furthermore, CKMM AA genotype was associated with high values of VO2(max) (AA - 58.98 (3.44) ml/kg/min, GA - 56.99 (4.36) ml/kg/min, GG - 52.87 (4.32) ml/kg/min, p = 0.0097). Thus, CKMM gene A/G polymorphism is associated with physical performance of athletes.     

An association between − 866G/A polymorphism in the promoter of UCP2 and obesity: A meta-analysis

− 866G/A polymorphism in the promoter of UCP2 gene has been reported to be associated with obesity, but the results remain inconclusive. To assess the relation of UCP2 − 866G/A polymorphism and obesity susceptibility, a meta-analysis was performed. PubMed, ISI, Wanfang database, VIP and CBM were searched to identify relevant studies up to July 31, 2012. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using fixed or random effect models. Subgroup analysis was performed by ethnicity (categorized as Asian and European). Heterogeneity and publication bias evaluation were performed to validate the credibility. Meta-regression and the ‘leave one out’ sensitive analysis were used to explore the potential sources of between-study heterogeneity. 14 studies were included in this meta-analysis. After exclusion of articles that deviated from the HWE in controls, and were the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the A allele with reduced risk of obesity in overall analysis and in European in the dominant, codominant and additional models. In Asian, no significant association was found between the − 866G/A in UCP2 gene and obesity susceptibility. The meta-analysis suggested that UCP2 − 866G/A polymorphism was associated with obesity. The A allele may be an important protective factor for obesity in European, but not in Asian. Further studies are needed to elucidate the relationship.     

UCP-866G/A和ADIPQ+45T/G基因多态性的交互作用与2型糖尿病 合并冠心病发病风险的关系

目的：探讨UCP2-866G/A 和ADIPOQ+45T/G 基因多态性的交互作用与2型糖尿病合并冠心病发病风险的关系。方法：随机 选取2014 年10 月至2015 年5 月在佳木斯大学附属第一医院就诊的130 例单纯2 型糖尿病患者和128 例2 型糖尿病合并冠心 病患者进行病例对照研究。分别采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP）方法和聚合酶链反应- 高分辨率溶解曲 线（PCR-HRM）方法检测UCP2-866G/A 和ADIPOQ+45T/G 的基因多态性,并用非条件Logistic 回归分析两基因间的交互作用。 结果：在两组间分别进行UCP2-866G/A 和ADIPOQ+45T/G 基因多态性的单独关联分析,两变异位点的基因型和等位基因的频率 在两组间的分布及遗传模型关联分析均无统计学差异（P>0.05）。两变异位点联合分析发现,UCP2-866 G/A 的GG、GA 分别和 ADIPOQ+45T/G 的TG 在2 型糖尿病合并冠心病中存在正向交互作用（P=0.000,ORI=ORAB/(ORA× ORB)=30.533/(0.549× 0.116) >1;P=0.007,ORI= ORAB/(ORA× ORB)=13.914/(0.525× 0.116)>1。结论：该研究显示： UCP-866G/A 和ADIPOQ+ 45T/G 单一基因的 多态性与2 型糖尿病合并冠心病患病风险无关,而两者之间的交互作用可能增加2 型糖尿病合并冠心病的发病风险。     

Association of a polymorphism of the CC chemokine receptor-2 gene with bone mineral density

The possible association of the 190G-->A (Val64Ile) polymorphism of the CC chemokine receptor-2 gene (CCR2) with bone mineral density (BMD) was examined in 2215 subjects (1125 men, 1090 women), all of whom were community-dwelling individuals aged 40 to 79 years. Among men aged < 60 years, BMD for the distal radius, lumbar spine, or Ward's triangle was significantly greater in those with the AA genotype than in those with the GG or GA genotypes. For postmenopausal women, BMD for the distal radius or femoral neck was significantly greater in those with the AA genotype than in those with the GG or GA genotypes. In contrast, for men aged > or =60 years and for premenopausal women, BMD was not associated with the CCR2 genotype. These results suggest that CCR2 may be a new candidate for a susceptibility locus for bone mass in middle-aged men and postmenopausal women.     

Effect of g.2728g > A and g.3996t > C polymorphisms at the leptin gene locus on microstructure and physicochemical properties of longissimus lumborum muscle of Polish Landrace pigs

The influence ofHindIII (g.2728G > A) and Bg/II (g.3996 T > C) polymorphisms at the leptin gene locus on muscle fibre characteristics and meat quality of longissimus lumborum muscle was studied in 146 barrows of the Polish Landrace breed. Leptin gene polymorphism was identified by PCR-RFLP. Fibre type percentage, fibre diameter and the following technological parameters ofmeat were also determined: pH45, pH24, L*a*b* colour, drip loss, water holding capacity, shear force and intramuscular fat content. Polymorphism was not detected in the locus studied in the Landrace pig herd analysed with the Bg/II restriction enzyme (g.3996 T > C). For the HindIII enzyme (g.2728G > A), there was a high frequency of GG homozygotes (0.78) and G allele (0.89), but the AA genotype was not present. Moreover, the genotypes ofleptin gene RFLP-HindIII polymorphism had no effect on intramuscular fat content and muscle fibre type percentage, but had a significant effect on muscle fibre size. Heterozygous GA fatteners had a significantly larger (P < 0.05) diameter of type IIB and type I fibres compared to homozygous GG fatteners. Generally, meat quality parameters were comparable among the examined genotypes except for water holding capacity (which was the lowest for the GG genotype) and colour lightness (L*) (which was the lightest for GA genotype). Moreover, regardless of genotype, large differences were observed between each animal in the distribution of intramuscular fat.     

Retracted: Rs11655237 polymorphism of LINC00673 affects the prognosis of cervical cancer by interfering with the interaction between LINC00673 and microRNA-1231

Single-nucleotide polymorphism (SNP) in long noncoding RNAs (lncRNAs) is known to disrupt the binding between lncRNAs and microRNAs. In this paper, we aimed to explore the role of LINC00673 rs11655237 SNP in the survival of cervical cancer (CC). Real-time polymerase chain reaction and western-blot analysis were used to detect expressions of LINC00673 and microRNA-1231 (miR-1231) in CC patients with different rs11655237 SNP genotypes. And the expression of LINC00673, miR-1231, and IFNAR1 was measured in mice and cells treated with exosomes carrying GG, GA, and AA rs11655237 genotypes. Compared with patients carrying the rs11655237 A allele of LINC00673 rs11655237 SNP, patients carrying the G allele showed higher overall survival and higher miR-1231 expression. In addition, the expression of miR-1231 was the highest in patients carrying the GG genotype and the lowest in patients carrying the AA genotype. Furthermore, the exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP reduced tumor growth in mice, while the inhibitory effect of rs11655237 A allele was much stronger than that of the rs11655237 G allele. Additionally, exosome treatment upregulated the expression of LINC000673 and IFNAR1 while downregulating the expression of miR-1231. Interestingly, the A allele of rs11655237 generated a binding site for miR-1231 and subsequently affected the expression of IFNAR1, a target gene of miR-1231 containing a miR-1231 binding site in its 3′-untranslated region. Cells transfected with exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP achieved higher LINC000673 and IFNAR1 expression along with lower miR-1231 expression. Therefore, rs11655237 can be used as a prognostic biomarker for CC.     

Association between a single nucleotide polymorphism in the bovine chemerin gene and carcass traits in Qinchuan cattle

Qinchuan is a red or yellow draft and beef breed in China. In order to identify a predictor of carcass traits on the basis of associations between carcass traits and gene polymorphism, variation in the bovine chemerin gene was investigated using PCR-single-strand conformational polymorphism and DNA sequencing. An SNP of A868G located in exon 2 of the Bos taurus chemerin gene was detected in 716 samples of six breeds (Jiaxian red, Luxi, Nan yang, Qinchuan, Simmental and Luxi crossbred steers, and Xia'nan), all in China, and three genotypes (AA, AG and GG) were found. Based on the χ(2) test, the AA/AG/GG genotype frequencies of all six breeds were found to be in Hardy-Weinberg equilibrium. A possible association of A868G with some carcass traits was investigated in 106 Qinchuan cattle. Animals with the AG genotype were found to have significantly lower mean loin eye area and meat tenderness compared to those with the AA and GG genotypes. However, there was no significant association between any individual haplotype and backfat thickness, water holding capacity or marbling score. We suggest that A868G could be used as a molecular marker in marker-assisted selection for carcass traits.     

Polymorphisms of the myostatin gene and its relationship with reproduction traits in the bian chicken

Myostatin, or growth and differentiation factor 8, is a member of the transforming growth factor-β superfamily; it functions as a negative regulator of skeletal muscle development and growth in mammals. In this study, single nucleotide polymorphisms in the 5' regulatory region and exon 1 of the myostatin gene were detected by PCR-SSCP in the Bian, Jinghai, Youxi, and Arbor Acre chickens, and the associations of the polymorphisms with reproduction traits were analyzed. Seven SNPs (A326G, C334G, C1346T, G1375A, A1473G, G1491A, and G2283A) were found in the myostatin gene. Association analysis showed that the G2283A were significantly associated with reproduction traits. Bian chickens of the GG genotype had a greater age at first egg than those of the GA and AA genotypes (P?相似文献   

粘蛋白MUC1 568A/G SNP与辽宁地区人群胃癌遗传易感性的关系

为了探讨粘蛋白(MUC1)基因568位点A/G单核苷酸多态性与胃癌遗传易感性的关系, 采用序列特异性引物-聚合酶链反应(Sequence specific primers PCR, PCR-SSPs)检测来自辽宁地区人群138例胃癌患者及与其配比的131例对照个体MUC1 568 位点A/G多态性, 以ELISA法检测血清H. pylori IgG抗体。结果显示:(1)对照人群MUC1基因568位点AA、AG、GG 3种基因型分布频率分别为73.3%、22.1%、4.6%; (2)胃癌组MUC1 AA基因型携带频率显著高于正常对照组(P=0.03), 携带MUC1 AA基因型个体胃癌的发病风险增高到1.92倍; (3)以MUC1 AG+GG基因型并血清幽门螺杆菌(H. pylori)IgG抗体阴性的个体为对照, AG+GG基因型并H. pylori IgG抗体阳性个体、AA基因型并H. pylori IgG抗体阴性个体、AA基因型并H. pylori IgG抗体阳性个体胃癌患病风险增高, 但3组各组间差异均无统计学意义(P>0.05)。说明MUC1基因568位点A/G多态与胃癌的遗传易感性相关; MUC1 A/G基因多态性和H. pylori感染在胃癌发生发展过程未见交互作用。     

Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients

Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.