Tobacco Addiction and Pharmacogenetics of Nicotine Metabolism

This paper presents a brief overview of several components of tobacco addiction, including: 1) the epidemiology of smoking in the United States and elsewhere around the world; 2) implications of the pharmacogenetic study of nicotine metabolism for understanding tobacco addiction and its treatment; 3) the use of the twin design as an example of one strategy to understand the contribution of genetic and environmental factors to the pharmacokinetics of nicotine metabolism; 4) results from recent genomic studies of tobacco addiction in adults; and 5) a discussion of progress (past and future) toward the development of a comprehensive understanding of the pharmacogenetics of tobacco addiction and its treatment.     

Longitudinal Genetic Analysis of Menstrual Flow, Pain, and Limitation in a Sample of Australian Twins

Genetically informative longitudinal data about menstrual disorders allow us to address the extent to which the same genetic risk mechanisms are operating throughout the reproductive life cycle. We investigate the relative contributions of genes and environment to individual differences in menstrual symptomatology reported at two waves, 8 years apart, of a longitudinal Australian twin study. Twins were questioned in 1980–1982 and 1988–1990 about levels of menstrual pain, flow, and perceived limitation by menses. Longitudinal genetic analysis was based on 728 pairs (466 MZ and 262 DZ) who were regularly menstruating at both survey waves. A bivariate Cholesky model was fitted to the two-wave data separately for flow, pain, and limitation variables. The baseline model comprised common genetic and environmental factors influencing responses at both waves and specific effects influencing only the second-wave response. We also included age as a covariate in the model. Proportions of the longitudinally stable variance in menstrual flow, pain, and limitation attributable to genetic and individual environmental effects were calculated for the best-fitting models. Genetic factors accounted for 39% of the longitudinally stable variation in menstrual flow, 55% for pain, and 77% for limitation. The remaining stable variance was due to individual environmental factors (61, 45, and 23%, respectively). Therefore the stable variance over the 8-year interval was largely environmentally influenced for menstrual flow, was approximately equally determined by genetic and by nonshared environmental influences in the case of pain, and was due almost entirely to genetic influences for limitation by periods. We demonstrate for the first time that the same genetic influences are operative throughout the reproductive life span.     

The Genetic and Environmental Etiology of High Math Performance in 10-Year-Old Twins

The genetic and environmental etiology of high math performance (at or above the 85%tile) was examined in a population-based sample of 10-year-old twins (nMZ = 1,279, nDZ = 2,305). Math skills were assessed using a web-based battery of math performance tapping skills related to the UK National Math Curriculum. Probandwise concordance rates and liability threshold models indicated that genetic and shared environmental influences were significant, and that these estimates were generally similar to those obtained across the normal range of ability and did not vary significantly by gender. These results suggest that the genetic and environmental influences at the high end of ability are likely to be continuous with those that affect the entire range of math performance across all children irrespective of gender. Edited by Claire Haworth.     

Genetic Analyses of Maternal and Teacher Ratings on Attention Problems in 7-year-old Dutch Twins

The goal of the present study is to examine genetic and environmental influences on maternal and teacher ratings of Attention Problems (AP) in 7-year-old children. Teachers completed the Teacher Report Form (N = 2259 pairs), and mothers the Child Behavior Checklist (N = 2057 pairs). Higher correlations were found in twins rated by the same teacher than in twins rated by different teachers. This can be explained by rater bias or by a greater environmental sharing in twins, who are in the same classroom. We further found that 41% of the variation in maternal and teacher ratings is explained by a common factor. The heritability of this common factor is 78%. The heritabilities of the rater specific factors of mothers and teachers are 76% and 39%, respectively. Because Attention Problems that are persistent over situations may indicate more serious behavior problems than context dependent Attention Problems, we believe that gene finding strategies should focus on this common phenotype.Edited by Richard Rose     

酒精依赖者抑郁情绪与酒瘾的相关研究

目的探讨酒精依赖者抑郁情绪与酒瘾的关系。方法对50例酒精依赖、酒精所致精神障碍的患者进行抑郁自评量表(SDS)和密西根酒精依赖调查表(MA ST)评定,比较有抑郁组和无抑郁组的MA ST得分,并对结果进行相关和回归分析。结果酒精依赖者抑郁症状检出率为56%,抑郁组MA ST得分高于无抑郁组(t=3.37,P=0.002),SDS与MA ST相关系数(r=0.621),抑郁情绪对酒瘾的影响度达38.58%。结论酒瘾与抑郁情绪有密切关联,而抑郁情绪与负性生活事件有关。     

育龄期女性骨代谢与碘摄入过量及甲状腺功能亢进之间的关系研究

目的 观察伴有碘摄入过量或伴有甲状腺功能亢进育龄期女性骨密度及骨代谢指标的变化,探讨碘摄入量及甲状腺功能对育龄期女性骨密度及骨代谢指标的影响.方法 从2500例体检育龄期女性汇总筛选出30例健康育龄期女性,30例伴有甲状腺功能亢进育龄期女性,和30例伴有碘摄入过量育龄期女性,该三种不同状态育龄期女性分别归为对照组、甲亢组和碘摄入过量组.采用双能X线检测仪检测了各组育龄期女性骨密度(BMD)及血清骨代谢指标[骨碱性磷酸酶(BAKP)、骨钙素(OSC)、I型胶原交联羧基末端肽(ICTP)、甲状旁腺素(PTH)和25-(OH) D]的变化.结果 与对照组相比,甲亢组及碘摄入过量组腰椎(L2-4)和右侧桡骨中远1/3处的BMD水平均显著降低(P<0.05);与对照组相比,甲亢组ICTP、BAKP与OSC均显著增加(P< 0.05),碘摄入过量组的ICTP、BAKP、OSC水平则均显著降低(P<0.05),但两组的25-(OH) D和PTH水平无明显改变(P>0.05).结论 伴有碘摄入过量及甲状腺功能亢进的育龄期女性无继发性甲状旁腺功能亢进,无维生素D代谢异常,但有骨代谢失衡(即骨吸收与骨形成失衡)及骨密度降低异常.临床上育龄期女性若出现甲亢或长期碘摄入过量时,应提早治疗或调整以防止骨密度降低即骨质疏松的发生.     

女性流动人口的流动性、抑郁情绪与烟酒使用行为的关系

目的：考察女性流动人口的流动性、抑郁情绪与娴酒使用行为之间的关系。方法：运用问卷调查法对866名从农村流动到北京打工的年轻女性流动人口的流动性、抑郁情绪和烟酒使用行为进行测查。结果：①20．9％的女性流动人口使用一种或两种物质，20-25岁的女性流动人口使用两种物质的人数最多；②女性流动人口抑郁情绪的发生率为22．6％，未婚者的抑郁发生率显著地高于已婚者；③在总体流动时间（P〈0．05）和流动城市数量（P〈0．000）上存在显著的烟酒使用行为、年龄和教育水平的交互作用：在抑郁情绪上存在显著的烟酒使用行为主效应（P〈0．05）；④多层线性回归方程结果表明，在控制了婚姻、年龄和教育水平的作用后。女性流动人口的流动性、抑郁情绪可以显著地预测其烟酒使用行为。结论：女性流动人口的烟酒使用行为与其流动性和抑郁情绪有关，应该对女性流动人口的心理健康状况给予积极的关注。以促进她们的身心健康。     

糖、脂类、C反应蛋白与冠心病患者Gensini积分的相关性研究

目的 探讨糖、脂类、C反应蛋白与冠心病患者Gensini积分的相关性.方法 冠心病组选择我院2013年1月至2015年1月收治的冠状动脉硬化性心脏病患者60例,健康组选择我院体检中心同期体检的健康体检者60例,测定总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)、超敏C反应蛋白(CRP)、糖化血红蛋白(HbA1c),并且分析糖脂代谢指标和冠脉病变严重程度、CRP之间的关系.结果 ①与健康组对比,冠心病组HbA1c、TC、TG、LDL-C和HbA1c×LDL-C/HDL-C明显升高,HDL-C明显降低,数据比较差异具有统计学意义,P ＜0.05.②冠心病患者糖脂代谢指标与Gensini积分、CRP的相关性分析显示,HbA1c、LDL-C水平、HbA1c×LDL-C/HDL-C和Gensini积分、CRP呈正相关关系,HDL-C水平和Gensini积分、CRP呈负相关.结论 糖脂代谢与冠状动脉硬化性心脏病患者病情、血清C反应蛋白水平正相关,通过糖脂代谢指标能够对冠状动脉硬化性心脏病患者的病情和血清C反应蛋白进行一定的预测,具有临床检测价值.     

加巴喷丁治疗酒依赖的临床疗效

目的 观察加巴喷丁治疗酒精依赖的临床疗效。方法 选取2018年2月~2019年2月我院收治的酒依赖患者82例,采用随机数字表法分为加巴喷丁组和安慰剂组,每组41例。加巴喷丁组予加巴喷丁胶囊治疗,安慰剂组予无药物成分的模拟胶囊治疗,比较两组治疗前和治疗后2、4、8、12周强制性饮酒问卷（OCDS）、宾夕法尼亚酒精渴求量表（PACS）及副反应量表（TESS）评分。结果 治疗后2周,加巴喷丁组OCDS、PACS评分与安慰剂组比较,差异无统计学意义（P＞0.05）;治疗后4、8、12周,加巴喷丁组OCDS评分、PACS评分低于安慰剂组[（52.64±1.56）分vs（53.68±1.86）分、（18.62±5.22）分vs（24.34±5.65）分]、[（49.31±1.32）分vs（51.62±1.93）分、（15.14±4.15）分vs（23.92±4.86）分]、[（46.52±1.43）分vs（51.62±1.93）分、（14.71±5.67）分vs（23.92±4.86）分],差异有统计学意义（P＜0.05）;治疗后4、8、12周,两组TESS评分比较,差异无统计学意义（P＞0.05）。结论 加巴喷丁可有效减少饮酒行为,降低渴求度,且耐受性好,不良反应轻微。     

Genetic and Social Determinants of Initiation and Age at Onset of Smoking in Australian Twins

Retrospective data on age at onset of smoking, reported by 3810 adult Australian twin pairs, were analyzed to determine the role of genetic and environmental factors in the onset of smoking. Results of nonmetric multidimensional scaling supported a two-process model in which different etiologic factors determined which individuals were at risk of becoming smokers and the age at onset of smoking in those who were at risk. Parametric model-fitting confirmed this difference. For female twins and younger male twins (aged 30 years or less), the onset of smoking was strongly influenced by genetic factors, with shared and nonshared environmental effects having a more modest impact. For older male twins, shared environmental influences on onset of smoking were very important, and the influence of genetic predisposition was slight. The age at which smoking onset occurred, however, was influenced by both genetic and nonshared environmental effects, but not by shared environmental effects, in both sexes and both cohorts.     

早期合并促大脑代谢药物治疗酒精所致老年精神障碍的作用

目的:探讨早期合并应用促大脑代谢药物在酒精所致精神和行为障碍治疗中的作用。方法:将72例使用酒精所致精神和行为障碍的老年患者随机分为早期合并应用促大脑代谢药物配合地西泮、奥氮平治疗组(研究组36例)和单纯使用地西泮、奥氮平治疗组(对照组36例),给予12周相应的治疗。分别于治疗前及治疗2、4、8、12周采用中文版简易智能状态检查(MMSE)、阳性症状与阴性症状量表(PANSS)、临床疗效总评量表病情严重程度(CGI-SI)、治疗时出现的症状量表(TESS)进行评定;患者出院后随访6及12个月观察患者的社会功能恢复情况及复饮率。结果:研究组和对照组分别有34例和32例完成12周疗程。治疗前两组患者的MMSE、PANSS评分差异无统计学意义;治疗后两组各时间点MMSE评分较前提升、PANSS评分较治疗前明显下降(P均0.01)。治疗2~4周末研究组MMSE评分明显高于对照组、PANSS评分明显低于对照组(P均0.01);8~12周两组间各量表评分及疗效比较差异无统计学意义。治疗6及12个月时研究组社会功能恢复情况显著高于对照组(χ~2=4.942,7.675;P均0.01);12个月时复饮率研究组显著低于对照组(χ~2=9.021,P0.01)。结论:早期合并应用促大脑代谢药物配合地西泮、奥氮平治疗能够更快地改善使用酒精所致精神和行为障碍患者的记忆及智能情况,提高患者的社会功能恢复程度,降低复饮率。     

基于血液酒精浓度和脑电特征的酒后驾车事故倾向对比研究

为研究驾驶员不同程度饮酒后的交通事故倾向,结合步进酒后状态诱发和模拟驾驶实验,对比分析了驾驶员血液酒精浓度BAC和规范化脑电δ波功率增益NPG分别与交通事故倾向NAP之间的数值关系.实验结果显示:饮入酒精导致约92％驾驶员安全驾驶能力下降,但约8％驾驶员在适量酒精作用下反而有所提高,说明血液酒精浓度方案缺乏一定的严谨性;NPG与NAP之间普遍存在增减一致性,而BAC与NAP在约10％～30％主观最大饮酒量区间可能增减不一致.规范化脑电8波功率增益相比于血液酒精浓度能更准确的反映驾驶员不同程度饮酒后的交通事故倾向,可作为酒后驾车相关问题及对策研究的一种新型参数依据.     

糖代谢异常孕妇血清脂联素、C反应蛋白水平与围产儿结局的关系

探讨妊娠期糖代谢异常孕妇血清脂联素（APN）和C反应蛋白（CRP）水平与围产儿结局的关系。测定178例妊娠期糖尿病（GDM）患者、154例妊娠期糖耐量受损（GIGT）孕妇血清APN和CRP水平,记录孕妇年龄、孕产次、分娩孕周及并发症等,跟踪比较分析两组围产儿结局的差异。结果显示,GDM组的APN为5.45±2.97mg/L、CRP为8.53±2.47 mg/L,与GIGT组APN（8.96±3.12 mg/L）、CRP（4.50±1.49 mg/L）相比较,差异有统计学意义（P〈0.05）;GDM组巨大儿和新生儿低血糖的发生率明显高于GIGT组,差异有统计学意义（P〈0.05）;两组新生儿窒息、高胆红素血症发生率差异均无统计学意义。结论：随糖耐量异常进展,孕妇血清APN水平逐步下降,CRP水平逐步上升,这可导致不良围产儿出生率的增加,尤其是巨大儿和新生儿低血糖。本实验提示APN、CRP可能是调节胎儿宫内发育的候选因子。     

初诊2型糖尿病患者甲状腺激素水平与糖代谢水平的关系研究

目的 探究初诊2型糖尿病(T2DM)患者甲状腺激素水平与糖代谢水平的关系及其临床价值.方法 选取2014年6月至2016年6月我院内分泌科收治的96例T2DM患者,测定所有患者甲状腺激素水平和糖代谢水平,采用Spearman相关分析其相关性.结果 不同性别在甲状腺激素水平及糖代谢指标及血脂指标差异不具有统计学意义(P＞0.05).随着FPG升高,TSH、T3等激素水平降低,差异具有统计学意义(P＜0.05).随着TSH水平升高,FPG、2h PG、HbA1c、HoMA-IR、TC和TG差异具有统计学意义(P＜0.05).FT3与BMI、FPG、2h PG、HbA1c呈负相关(r=-0.453、-0.522、-0.621、-0.461,P＜0.05),FT3、FT4和TSH与HoMA-IR呈正相关(r=0.861、0.701和0.746,P＜0.05),TSH与HbA1c呈负相关(r=-0.622,P＜0.05),TT3和TT4与BMI、FPG、2h PG、HbA1c、HoMA-IR、TC和TG无相关性(P＞0.05).结论 初诊2型糖尿病患者甲状腺激素水平对患者糖代谢水平评估具有重要意义.     

Genetic and Environmental Mediation Between Measures of Personality and Family Environment in Twins Reared Together

In this study we analyzed the etiology of the relationship between personality traits and retrospectively recalled family environment. The data of 226 identical and 168 fraternal twin pairs reared together from the Jena twin study of social attitudes were available. Personality traits were measured using the self- and peer report versions of the German NEO-personality inventory-revised. A German version of Blocks Environmental Questionnaire was applied to measure two broad dimensions of the family environment retrospectively: support and organization. We could replicate earlier findings that retrospective reports of these family environment dimensions were in part genetically influenced. A total of 66% of the genetic variance in support and 24% in organization could be accounted for by heritable variance in self-rated personality. That was replicated by using peer reports of personality, 41% explained genetic variance in support and 17% in organization. Environmental mediations were negligible. This indicates that the relationship between personality and retrospectively recalled family environment is largely genetically mediated.

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the “classical” method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10–23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.     

Genetic and Environmental Contributions to the Correlation Between Alcohol Consumption and Symptoms of Anxiety and Depression. Results from a Bivariate Analysis of Norwegian Twin Data

Two thousand five hundred seventy pairs of Norwegian MZ and like-sexed and unlike-sexed DZ twins aged 18–25 years completed questionnaires with information about symptoms of anxiety and depression and alcohol consumption. The aim of the study was to estimate sex-specific genetic and environmental effects unique to symptoms of anxiety/depression and to alcohol consumption and effects common to the two phenotypes. Five models fitted the data almost equally well. The heritability estimate from these models ranged from .23 to .57 for male alcohol consumption, from .39 to .59 for female alcohol consumption, from .25 to .48 for male anxiety/depression, and from .45 to .56 for female anxiety/depression. The phenotypic correlation between alcohol and anxiety/depression in males (r = .23) could be fully explained by common genetic effects. The correlation in females (r = .18) was caused by individual environmental factors together with either genetic effects or family environment.     

COPD患者血脂代谢水平和hs-CRP水平关系的分析

目的:进行慢性阻塞性肺病(COPD)患者血脂代谢水平和hs-CRP水平关系的分析.方法:利用生化法测定了96例COPD患者血脂代谢水平,免疫比浊法测定了血清hs-CRP水平,并与68例正常对照组进行了比较.结果:96例COPD患者的血浆TC、TG、HDL-C、LDL-C和Lp(a)较之68例正常对照组明显降低,TC和L...     

IL-6及Sgp80、Sgp130与Graves'病及其骨代谢关系的临床研究

目的:探讨IL-6及其可溶性受体(Sgp80、Sgp130)与Graves'病(GD)及其骨代谢的关系.方法:对78例GD患者的血清行双抗体放射免疫分析检测血清IL-6,ELISA检测血清Sgp80、Sgp130.采用双能X线骨密度测定仪测定骨密度.结果:未治疗组、部分缓解组、缓解组的血清IL-6、Sgp130均明显高于正常对照组(P＜0.05),未治疗组、部分缓解组的血清Sgp80明显高于缓解组和正常对照组(P＜0.05).血清Sgp80与FT3、FT4、血磷(P)、血骨钙素(BGP)、尿羟脯胺酸(HYP)均成正相关.结论:血清IL-6及Sgp80、Sgp130与GD及其骨代谢的发病密切相关,血清Sgp80可作为观察GD治疗情况的重要指标,GD患者的皮质骨、松质骨有均等机会发生骨量丢失,骨形成与骨吸收的增加可能均为原发性的,而非骨形成继发于骨吸收.