SULT1A1 copy number variation: ethnic distribution analysis in an Indian population

Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes involved in metabolism of numerous xenobiotics, drugs and endogenous compounds. Interindividual variation in sulfonation capacity is important for determining an individual’s response to xenobiotics. SNPs in SULTs, mainly SULT1A1 have been associated with cancer risk and also with response to therapeutic agents. Copy number variation (CNVs) in SULT1A1 is found to be correlated with altered enzyme activity. This short report primarily focuses on CNV in SULT1A1 and its distribution among different ethnic populations around the globe. Frequency distribution of SULT1A1 copy number (CN) in 157 healthy Indian individuals was assessed using florescent-based quantitative PCR assay. A range of 1 to >4 copies, with a frequency of SULT1A1 CN =2 (64.9%) the highest, was observed in our (Indian) population. Upon comparative analysis of frequency distribution of SULT1A1 CN among diverse population groups, a statistically significant difference was observed between Indians (our data) and African-American (AA) (p =?0.0001) and South African (Tswana) (p SULT1A1 varies significantly among world populations and may be one of the determinants of health and diseases.     

The Epilepsy Genetic Association Database (epiGAD): Analysis of 165 genetic association studies, 1996–2008

We have created the Epilepsy Genetic Association Database (epiGAD, http://www.epigad.org , an online database of epilepsy genetic association studies. A systematic search using several search engines identified 165 studies. Herein we analyze the types of studies available, the sample sizes used, and the strength of the findings. Common questions examined were susceptibility to idiopathic generalized epilepsy, focal epilepsy, or febrile seizures, and pharmacogenomic approaches to drug‐resistant epilepsy. Sample sizes were generally small; 80% of studies had 200 or fewer cases, although more recent studies published from 2005–2008 incorporated slightly larger sample sizes. No association was judged as “strong” using current criteria for assessing genetic associations—this is probably due to inadequate sample sizes. Sample sizes need to increase, either by research collaboration or via systematic reviews and meta‐analyses. We believe epiGAD will facilitate future meta‐analyses.     

基于肿瘤临床前模型建立头颈癌新型药物基因组学的必要性及展望

头颈癌是全球第七大恶性肿瘤类型,超过60%患者初次确诊即为中晚期。靶向治疗和免疫治疗的发展已经显著推动了头颈癌治疗策略的转型,但是临床获益有待进一步提升。肿瘤临床前模型保留了患者肿瘤的基因和表型的异质性,已广泛应用于临床前药物筛选和验证体系。药物基因组学通过将基因组学和药物响应进行匹配,能够基于肿瘤异质性基础进行患者分层,优化治疗策略并挖掘新治疗靶点。本文概述药物基因组学的发展史,从头颈癌治疗现状和异质性特征出发,探讨借助临床前模型开展新型药物基因组学的必要性和可行性。     

沐舒坦临床应用剂量规范化探讨

沐舒坦作为一种粘液溶解剂,临床应用广泛。然而,沐舒坦的临床应用剂量的选择跨度较大,疗程长短也存在差异,还未能达成共识。其疗效与剂量的相关性有待于临床实验探究。随着遗传药理学和药物基因组学的兴起,研究沐舒坦是否存在遗传和基因组因素的影响,可能为其临床应用剂量的选择及个体化用药开拓新的视野。     

Migraine headache: a review of the molecular genetics of a common disorder

This tutorial summarises the state-of-the-art on migraine genetics and looks at the possible future direction of this field of research. The view of migraine as a genetic disorder, initially based on epidemiological observations of transmission of the condition within families, was subsequently confirmed by the identification of monogenic forms of “syndromic” migraine, such as familial hemiplegic migraine. We are currently witnessing a change in the way genetic analysis is used in migraine research: rather than studying modalities of inheritance in non-monogenic forms of migraine and in the persistent modalities of migraine headache, researchers are now tending to focus on the search for genetic markers of dysfunction in biological systems. One example of the evolution of migraine genetic research is provided by the recent efforts to shed light on the pharmacogenomic mechanisms of drug response in migraineurs. In addition, novel molecular approaches about to be introduced are expected to further increase knowledge on this topic and improve patient management.     

基于药物基因检测使用文拉法辛治疗抑郁症的临床效果

目的探讨药物基因检测下使用文拉法辛治疗抑郁症的效果和安全性,为个体化用药提供参考。方法纳入符合《国际疾病分类(第10版)》(ICD-10)抑郁发作诊断标准的66例患者为研究对象。将药物基因检测报告建议并选用文拉法辛治疗的患者分为研究组(n=32),医生与患者协商后决定使用文拉法辛治疗的患者为对照组(n=34)。于治疗前及治疗2、4、6、8周末使用汉密尔顿抑郁量表24项版(HAMD-24)评定临床疗效,于治疗前及治疗8周末使用席汉残疾量表(SDS)评定患者的社会功能,于治疗后采用副反应量表(TESS)评定不良反应发生情况。结果治疗4、6、8周末,研究组HAMD-24评分均低于对照组,差异均有统计学意义(t=2.344、4.316、5.760,P0.05或0.01);治疗8周末,研究组SDS评分低于对照组,差异有统计学意义(t=2.173,P0.05),研究组不良反应发生率低于对照组,差异有统计学意义(χ~2=5.720,P0.05)。结论基于药物基因检测使用文拉法辛治疗抑郁症,可能有助于改善患者的抑郁情绪,且安全性更好。