美托洛尔常规治疗与基因导向治疗高血压病的比较

比较基因导向美托洛尔个体化治疗与常规治疗高血压病的临床疗效、安全性和经济性。从300例1或2级原发性高血压患者中随机抽取165例进入常规治疗组（A组,n＝165）,其余135例患者进行CYP2D6基因、β1肾上腺素能受体（β1-AR）基因多态性检测,将β1-AR基因389位携带了Arg等位基因的原发性高血压患者133例分入基因导向治疗组（B组,n＝133）;基因导向治疗组患者按照CYP2D6基因分型分为弱代谢组（PMB,n=43）、中等代谢组（IMB,n=54）和强代谢组（EMB,n=36）。常规治疗组给予美托洛尔100mg/日,基因导向治疗组中PMB组、IMB组、EMB组分别给予美托洛尔25 mg/d、100mg/d、200mg/d,均分2次口服降压治疗,共随访8周,观察血压和不良反应等指标。应用成本-效果分析方法对基因导向型个体化治疗方案进行药物经济学评估。结果为基因导向治疗组降压总有效率明显高于常规治疗组（65.08% vs 47.4%, P＜0.05）;基因导向治疗组的不良反应发生率明显低于常规治疗组（P＜0.05）。成本效果分析,基因导向治疗组的平均成本效果比稍高于常规治疗组（350.05 vs 249.96）,与常规治疗组相比增量成本效果比（ICERs）为618.38。依据基因导向的前瞻性美托洛尔个体化降压治疗较传统给药模式更为安全、有效,但短期治疗难以体现其更优的经济学价值。     

Identifying the interaction of maternal sensitivity and two serotonin-related gene polymorphisms on infant self-regulation

During infancy, orienting and gaze aversion serve as major self-regulatory mechanisms and play an important role in the development of deliberate self-regulation and control. The present study examined the interaction of intrinsic factors (MAOA-uVNTR and 5-HTTLPR gene polymorphisms) and extrinsic factors (maternal sensitivity) on early infant self-regulatory behavior. We assessed 5-HTTLPR (ss + sl versus ll) and MAOA-uVNTR (3 and 4 among boys, and 3/3, 3/4, and 4/4 among girls) polymorphisms, determined maternal sensitivity during mother–child free play, and coded infant self-regulatory behavior (i.e., orienting shifts in a temperament test) in 281 six-month-old infants. We found that infants who experienced a lower level of maternal sensitivity and had the short allele of 5-HTTLPR variants and the 3/3 MAOA-uVNTR polymorphism displayed lower self-regulation capacity than did those infants with a higher level of maternal sensitivity. This finding suggested a modulatory role of maternal sensitivity. Moreover, these findings are consistent with the genetic vulnerability hypothesis, which states that beneficial environmental factors serve as a buffer against harmful genetic predispositions during child development.     

A genetic variant (COMT) coding dopaminergic activity predicts personality traits in healthy elderly

Association studies between the NEO five factor personality inventory and COMT rs4680 have focused on young adults and the results have been inconsistent. However, personality and cortical changes with age may put older adults in a more sensitive range for detecting a relationship. The present study examined associations of COMT rs4680 and personality in older adults.Genetic association analyses were carried out between the NEO and the targeted COMT rs4680 in a large, well-characterized sample of healthy, cognitively normal older adults (N = 616, mean age = 69.26 years).Three significant associations were found: participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039) and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006) than participants with AA or AG genotypes.These results suggest that older adults with higher COMT enzymatic activity (GG), therefore lower dopamine level, have lower Neuroticism scores, and higher Agreeableness and Conscientiousness scores. This is consistent with a recent model of phasic and tonic dopamine release suggesting that even though GG genotype is associated with lower tonic dopamine release, the phasic release of dopamine might be optimal for a more adaptive personality profile.     

From acting to communicating: The analysis of a boy with a pathological organization1

The author presents the analysis of an 8 year‐old boy prematurely born after a high‐risk pregnancy, then hospitalized for two weeks. He was never breastfed and presented vomiting, intense activity and inadequate behaviour as symptoms. His highly dysfunctional family is composed of a non‐productive father and a homely, though aggressive, mother. The patient displayed a rigid defensive structure with perverse aspects and a cruel superego. His constant interest in magical characters frequently disguises an avoidance of reality. By means of transference interpretations, a trustworthy link with the analyst now allows him his own mental space, where hidden psychotic states come to light. In the clinical material, this boy's skills for insight mingle with oscillations from severely defensive states to integration and vice versa. The analytic relationship in this often hostile scenario has become strong. The analysis is hampered by constant demands from family and school‐both expect the analyst to prevent his frequent acting out. Whereas some perverse polymorphism is part of childhood and may persist throughout life, it is likely that the patient's pathological organization may yield to reality and facilitate reparation, relinquishing the world of make‐believe as well as the intense projective mental functioning.     

NR3C1基因Bcl1多态性与青少年抑郁：压力性生活事件的调节作用

迄今,有关抑郁的基因×环境交互研究多数基于“单胺缺陷假说”,相对较少有研究以“HPA轴假说”为框架考察抑郁的遗传机制,且忽视了基因-环境相关的影响。本研究对1081名青少年进行追踪研究,考察NR3C1基因Bcl1多态性与压力性生活事件对抑郁的影响。结果发现,经历较多压力性事件时,C等位基因携带者的抑郁水平显著高于GG纯合子携带者;经历较少压力性事件时,不同基因型携带者的抑郁水平无差异。此外,通过区分独立性压力性事件和预测早期抑郁进一步排除了基因-环境相关的影响,在一定程度上验证了结果的可靠性。     

Genetic polymorphisms of alcohol-metabolizing enzymes and their association with alcoholism risk,personality and anthropometric traits among Malaysian university students

Three single nucleotide polymorphisms (SNPs) in alcohol-metabolizing genes – ADH1B (Arg47His), ADH1C (Ile350Val) and ALDH2 (Glu504Lys) have been extensively associated with flush reaction and alcoholism. Therefore, we investigated the association of these three SNPs with alcohol-induced reactions (AIRs), alcoholism risk, personality and anthropometric traits among Malaysian university students. AIRs, Self-Rating of the Effects of Alcohol (SRE) and Ten-Item Personality were surveyed, anthropometric measurements and DNA samples were taken. Among 264 valid drinkers (111 males, 153 females; 229 ethnic Chinese, 35 ethnic Indians), the minor allele frequencies for ADH1B, ADH1C, ALDH2 among Chinese/Indians were .45/.07, .33/.40, .32/.41, respectively; distribution of ADH1B alleles significantly different between ethnicities. Current/former experiences of flushing, hives, heart palpitations after alcohol consumption; and sleepiness, headache reactions, early and overall SRE were significantly different between ethnicities and genders, respectively. Overall SRE score was associated with ADH1C and ALDH2 alleles. ‘Openness to Experiences’ was associated with ALDH2 genotypes and alleles; Glu/Glu or Glu carriers showed significantly higher means. ADH1B Arg/Arg and Arg carriers showed significantly higher total body and subcutaneous fats but association was abolished after controlling for ethnicity. In conclusion, gender and ethnicity, but not alcohol-metabolizing gene variants, play a role in influencing the manifestation of AIRs.     

“God is the creator of all life and the energy of this world”: German intersex Christians’ reflection on the image of God and being created in God’s image

ABSTRACT

Intersex individuals are often told they are not human beings because they do not neatly fit into the categories of “female” and “male.” Many are made to feel like monsters. Christianity enforces this model of sexual dimorphism with the notion that to be a human being means to be created clearly “female” or clearly “male” in the image of God. This paper draws on interviews with German intersex Christians to explore their diverse images of God and what it means to be created in God’s image with the goal of creating new “conditions of possibility” that represent the full range of human sex/gender.     

Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population

Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case–control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24–1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16–2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49–3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31–2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations.     

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4^*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.