亚甲基四氢叶酸还原酶基因C677T突变、同型半胱氨酸水平与1型糖尿病微血管并发症相关性研究

国内外大量研究表明 ,高同型半胱氨酸 (Hcy)血症是心、脑及外周血管疾病的重要危险因素之一[1 ] 。亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T突变是导致该酶活性降低并引起高Hcy血症的主要遗传机制。 2型糖尿病 (DM)血管病变患者MTHFR基因C6 77T纯合突变率及Hcy水平明显升高[2 ,3] 。本研究旨在探讨MTHFR基因C6 77T突变、Hcy水平与 1型DM年轻患者糖尿病微血管并发症的关系。对象1型DM患者 6 8例 ,男 2 9例 ,女 39例 ,年龄 (17 2± 4 0 )岁 ,病程 (9 0± 3 4 )年 (5 0～ 18 5年 ) ,病例符合 1999年WHO的诊断标准。根据是否合…     

亚甲基四氢叶酸还原酶基因多态性与儿童急性淋巴细胞 白血病化疗中甲氨蝶呤毒性相关性的 meta 分析

目的评价亚甲基四氢叶酸还原酶(MTHFR)基因C 677 T位点多态性与儿童急性淋巴细胞白血病(ALL)化疗用药甲氨蝶呤(MTX)不良反应易感性的关联。方法计算机检索The Cochrane Library、Pub Med、EMbase、EMCC、OVID、CNKI、VIP和Wan Fang Data数据库,检索时间均为建库至2016年3月。2名研究者独立筛选文献、提取资料数据并评价纳入研究的偏倚风险后,采用Rev Man 5.3和Stata 12.0软件,分别以隐性、显性、共显性、加性和等位基因模型对基因多态性与MTX化疗时不良反应的关联进行meta分析。结果共纳入12项研究,均为病例-对照研究,其中病例组1 419例,对照组2 188例。Meta分析结果显示,纳入的研究中MTHFR基因多态性在5种分析模型下与ALL患儿予以MTX化疗时中性粒细胞减少、血小板减少、血红蛋白减少、黏膜损害以及肝功能损害的不良反应均无关联。共显性模型下,MTHFR基因多态位点C677T与MTX总不良反应易感性的关联具有统计学意义(OR=1.39,95%CI:1.02~1.91,P=0.04)。隐性基因模型下,MTHFR的C677T多态性和MTX化疗时胃肠道不良反应的发生风险减少有关(OR=3.31,95%CI:1.03~10.59,P=0.04)。显性基因模型下,MTHFR的C 677 T多态性和MTX化疗时皮肤损害不良反应的风险减少存在关联(OR=3.05,95%CI:1.25~7.41,P=0.01)。结论 MTHFR的C 677 T多态性和MTX化疗时不良反应并无显著关联,但仍需行更大样本研究分析。     

Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma

The authors investigated whether high-dose methotrexate-induced toxicity differed according to the presence of methylenetetrahydrofolate reductase (MTHFR) or reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15 children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were treated using protocols that included high-dose methotrexate (3.0 g/m), for an overall total of 43 courses. Methotrexate-induced toxicities and the plasma methotrexate concentrations were evaluated retrospectively. Hematologic toxicity was the most frequently observed toxicity, appearing in 87% of the patients. In a subset of patients (47%), elevation of liver transaminase levels showed a repeated tendency to develop. High plasma methotrexate concentrations at 48 hours after the methotrexate infusion were not significantly related to methotrexate-induced toxicities except for mucositis. A generalized estimating equation analysis revealed that vomiting during the high-dose methotrexate treatment was more pronounced in patients who had a larger number of G alleles at the RFC1 80G>A polymorphism. No significant differences in the development of other toxicities or in the plasma methotrexate concentrations were observed for the different MTHFR 677C>T or RFC1 80G>A polymorphisms. This study suggests but does not prove that the RFC1 80G>A polymorphism may contribute to interindividual variability in responses to high-dose methotrexate.     

TV watching modifies obesity risk linked to the 27Glu polymorphism of the ADRB2 gene in girls.

OBJECTIVE: A matched case-control study was conducted in a population of Spanish children and adolescents (5-18 years old), to assess the interaction between the Gln27Glu polymorphism of the ADRB2 and television (TV) watching on obesity risk. PATIENTS: Obese (n=165) and control subjects (n=165) matched by sex and age were recruited and classified according to Spanish reference data. Results. Using conditional logistic regression, we calculated the obesity risk linked to the polymorphism. A statistically significant association was found for 27Glu carrier allele girls (OR = 1.95; 95% CI = 1.02-3.70), but no association was apparent among boys. In the fully adjusted model, the odds ratio for obesity linked to the genotype Glu27Glu in the female population rose to 4.84 (95% CI = 1.37-17.10). Moreover, we found a significant negative interaction between hours of TV watching and the Gln27Glu polymorphism for obesity risk in girls. Surprisingly, among 27Glu carrier subjects, even girls with a low level of TV watching ( < 12.5 h/week) had a high obesity risk (OR = 4.60; 95% CI = 1.01-20.02), which was not very different to the odds ratio values for sedentary girls carrying the 27 Glu allele watching TV more than 12.5 h/week (OR = 6.05; 95% CI = 1.31-27.71). Conclusion. A higher risk of obesity was found for girls carrying the 27Glu allele of the ADRB2 gene even when they spent less than 12.5 h/week watching TV. In addition, our results suggest that the effect of sedentary lifestyle on obesity risk may depend on the genotype of the subject.     

急性淋巴细胞白血病患儿MTHFR基因多态性与大剂量甲氨蝶呤毒副反应的关系

目的：探讨亚甲基四氢叶酸还原酶（MTHFR）基因单核苷酸多态性对急性淋巴细胞白血病（ALL）患儿使用大剂量甲氨蝶呤（HD-MTX）化疗后毒副反应的影响。方法：应用RT-PCR-变性梯度凝胶电泳结合DNA测序技术,对52例ALL患儿MTHFR C677T、A1298C和G1793A基因型进行检测。按照国立癌症研究所常规毒性判定标准（NCI-CTC）对患儿HD-MTX化疗后的不良反应统一评价。结果：MTHFR 1298AC基因型患儿发生血小板减少的风险较AA型提高了13.7倍（OR=13.7,95%CI=1.18～159.36,P=0.036）。MTHFR C677T和G1793A各基因型发生各类HD-MTX化疗不良反应的差异无统计学意义（P>0.05）。结论：MTHFR A1298C多态性可能与ALL患儿HD-MTX化疗后的毒副反应相关。     

急性淋巴细胞白血病患儿亚甲基四氢叶酸还原酶多态性与氨甲蝶呤毒副反应的研究

氨甲蝶呤(MTX)是治疗儿童急性淋巴细胞白血病(ALL)的常用药物．在ALL维持治疗及髓外白血病的防治中有重要的作用。不同个体对MTX的敏感性及耐受性有很大差异。MTX是抗叶酸代谢药物，推测细胞内叶酸代谢状态的改变可能影响机体对MTX的敏感性。亚甲基四氢叶酸还原酶(methyleneteterabytrofolate reductase，MTHFR)是叶般代谢的关键酶，其基因中第677位C→T突变可降低酶括性，改变细胞内活性叶酸成分的分布，可能与机体对MTX的敏感性有关。     

Plasma visfatin and adiponectin concentrations in physically active adolescent girls: relationships with insulin sensitivity and body composition variables

The purpose of this study was to evaluate the associations of visfatin and adiponectin concentrations with insulin resistance and body composition in regularly physically active pubertal girls. In 129 girls, aged 13-15 years (pubertal stages 3-5), visfatin, adiponectin, insulin resistance measured by homeostasis model assessment (HOMA), and body composition measured by dual-energy X-ray absorptiometry were evaluated. Visfatin concentration was related to HOMA and overall adiposity (body mass index, fat mass) markers, whereas adiponectin concentration was related to overall adiposity (fat mass), central adiposity (trunk fat) and fat free mass values. These relationships remained significant (p < 0.05) after adjusting for pubertal stage. Visfatin was independently related to body mass index (beta = 0.936; p = 0.0001) and HOMA (beta = 0.444; p = 0.039) indices, whereas adiponectin was independently related to fat free mass (beta = 0.889; p = 0.003) and trunk fat (beta = -0.468; p = 0.042) values. In conclusion, visfatin could be related to insulin resistance and overall adiposity indices, whereas adiponectin was related to different body composition values in regularly physically active pubertal girls.     

Sleep fragmentation and intermittent hypoxemia are associated with decreased insulin sensitivity in obese adolescent Latino males

Background:Although sleep-related breathing disorder (SRBD) has been linked to insulin resistance in adults, this has not been as well established in children. We hypothesized that the severity of SRBD in adolescents was associated with metabolic impairment.Methods:Polysomnography was performed on obese, Latino males referred for snoring. The frequently sampled intravenous glucose tolerance test was used to assess glucose homeostasis. Total-body dual-energy X-ray absorptiometry was used to quantify adiposity.Results:A total of 22 males (mean age ± SD: 13.4 ± 2.1 y, BMI z-score 2.4 ± 0.3, obstructive apnea hypopnea index 4.1 ± 3.2) were studied. After correcting for age and adiposity in multiple-regression models, Log frequency of desaturation (defined as ≥3% drop in oxygen saturation from baseline) negatively correlated with insulin sensitivity. Sleep efficiency was positively correlated with glucose effectiveness (S(G), the capacity of glucose to mediate its own disposal). The Log total arousal index was positively correlated with Log homeostasis model assessment-estimated insulin resistance.Conclusion:Sleep fragmentation and intermittent hypoxemia are associated with metabolic impairment in obese adolescent Latino males independent of age and adiposity. We speculate that SRBD potentiates the risk for development of metabolic syndrome and type 2 diabetes in the obese adolescent population.     

Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls

Preterm birth might induce permanent changes in vascular structure and function as well as in blood pressure. To elucidate this hypothesis and underlying mechanisms in girls born before term, the authors correlated neonatal data, including estradiol levels, with vascular function and structure and with blood pressure after puberty. In a case-control study design, 34 girls born before term and 32 gender- and age-matched control infants born at term were included. Pulse wave analysis was used to determine aortic pressure profiles and overall arterial compliance. Stiffness of the carotid artery and abdominal aorta was measured with ultrasonography. Pulse wave velocity in the forearm was measured with photoplethysmography. A laser Doppler technique was used to determine skin perfusion before and after transdermal delivery of acetylcholine, an endothelium-dependent vasodilator. It was found that preterm girls had significantly higher brachial and aortic blood pressure, a narrower but less stiff abdominal aorta, and lower peripheral skin blood flow than did control infants. Augmentation index, carotid stiffness, pulse wave velocity, endothelium-dependent vasodilatation, and heart rate were similar in the two groups. In the preterm group, blood pressure and vascular functions showed no association with intrauterine growth retardation or neonatal estradiol levels. In conclusion, preterm girls have higher blood pressure and an increased resistance in the vascular tree after puberty. These findings may have implications for future cardiovascular risk in the growing adult population surviving preterm birth.     

Acute affective responses to prescribed and self-selected exercise intensities in young adolescent boys and girls

This study examined the patterning of acute affective responses to prescribed and self-selected exercise intensities in a young adolescent population. Twenty-two young adolescents (13.3 +/- .33 years) completed a maximal exercise test to identify ventilatory threshold (VT). Participants then completed two prescribed intensities (one set above and one below the VT) and a self-selected intensity. Pre-, during, and postexercise affective valence was measured. Results revealed that during exercise, affective valence assessed by the Feeling Scale (FS) remained positive in the self-selected and low-intensity conditions but declined in the high-intensity condition. Postexercise FS responses rebounded to preexercise levels, eradicating divergent trends that occurred during exercise.     

Waist circumference in relation to body perception reported by Finnish adolescent girls and their mothers

Aim: To study how waist circumference (WC) relates to body perception in adolescent girls and to maternal perception of the girl's body size.
Methods: Three hundred and four girls, 11–18 years, were measured for height, weight and WC. 294 girls provided self-report data on weight, height and body image before anthropometric measurements. Paired data from 237 girls and mothers on perception of the girls' body size were collected.
Results: In girls, self-reported weight indicated awareness of actual body size. The girls' body perception showed an overestimation of body size relative to international reference values for body mass index (BMI) (p < 0.05), but not for WC. Girls' body perception exceeded that of their mothers (p < 0.05). Maternal perception agreed better than the girls' perception with international reference values for BMI (p < 0.05). No significant difference between mothers and girls were found concerning agreement of body perception with international reference values for WC.
Conclusion: WC rather than BMI agrees with perception of body size, possibly due to its relation to abdominal fat at different ages. For effective prevention and treatment programmes for weight-related health problems among adolescent girls, we recommend measuring WC to diminish the discrepancy between measured and perceived body size.     

Pelvic ultrasonography in premenarcheal girls: relation to puberty and sex hormone concentrations.

Real time ultrasonography of the pelvic organs was performed on 114 normal premenarcheal girls aged between 2 years and 13 years 11 months. Values were obtained for total uterine length, anteroposterior diameters of the corpus and cervix, corpus/cervix ratio, and uterine and ovarian volumes and the resultant data were grouped according to age. It was concluded that there is no change in uterine size until approximately 7 years of age. Then the uterus begins to enlarge, both in prepubertal girls, in whom this is an age related function, and in pubertal girls, whose uterine growth is influenced not only by age but also by size and, independently of these two factors, by oestradiol concentrations. The onset of a modification in uterine morphology with a greater enlargement of the corpus than the cervix is also seen at age 7 years. Ovarian maturation begins in the very first years of life and, even in pubertal girls, seems to be influenced by age only and not by hormonal stimuli.