The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: A nested case‐referent study

Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study. Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study. Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance. Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.     

A population-based study of plasma cyclic guanosine monophosphate: relations to age,atrial natriuretic factor and angiotensin-converting enzyme activity

Solberg K, Rødningen OK, Tonstad S, Ose L, Leren TP. Familial hypercholesterolaemia caused by a non-sense mutation in codon 329 of the LDL receptor gene. Scand J Clin Lab Invest 1994;54:605-9

Analysis of single-strand conformation polymorphisms (SSCP) was employed to screen familial hypercholesterolaemia (FH) subjects for point mutations in exon 7 of the low density lipoprotein receptor (LDLR) gene. An abnormal band pattern was found in one out of 100 unrelated FH subjects. The underlying mutation was found by DNA sequencing to be due to heterozygosity (C/T) at nucleotide 1048. Nucleotide 1048 is the first nucleotide of codon 329, and is located within the domain that has a high degree of homology with the precursor for epidermal growth factor. The C → T transition, referred to as FH-Fossum, changes codon 329 from CGA_Arg to TGA_Stop. The mutation is expected to cause a class 1 receptor defect.     

心脑血管病患者P2Y1基因多态性与阿司匹林抵抗的相关性

目的 研究ADP受体P2Y1基因多态性与阿司匹林抵抗(aspirin resistance AR)是否存在相关性.方法 选取2010年10月至2012年3月上海交通大学附属第六人民医院急诊科急诊内科和心内科病房住院患者中40岁以上冠心病、高血压、脑梗死后合并或不合并2型糖尿病患者330例.入院后,进行详细病史采集、查体、及测定相关血液指标.服用阿司匹林(100 mg/d)至少7d后次日晨,抽取肘静脉血2管,光学法分别测定花生四烯酸(arachidonic acid,AA)及二磷酸腺苷(adenosine diphosphate,ADP)诱导的血小板聚集率,根据血小板聚集率,确定患者为AR或阿司匹林敏感(aspirin sensitive,AS).另一管置-80℃冰箱待集中后通过PCR扩增直接测序法检测P2Y1基因893及1622位点多态性.结果 AR者95例,发生率为28.79％;AS者235例,发生率为71.21％;基因测序结果相关性分析发现P2Y1基因的893C＞T变异与AR发生率增加有关OR=3.16 (95％CI1.36～7.16).与AS组临床资料相比AR组在以下3个方面差异具有统计学意义(P ＜0.05):AR组年龄大、糖尿病发生率高、HDL水平低,进一步使用从包括年龄、2型糖尿病、高血压等在内的各种可能的危险因素中通过Logistic回归分析筛选发现,2型糖尿病、高血压病和低HDL水平是发生AR的独立危险因素.结论 P2Y1基因的893C＞T变异与AR相关.年龄大,合并2型糖尿病,血HDL水平低者更易发生AR;合并2型糖尿病或高血压病,低HDL水平是发生AR的独立危险因素.     

北京人群高迁移率族蛋白B1基因多态性的分布及意义

目的检测高迁移率族蛋白BI（HMGB1）基因多态性在中国北京地区人群的分布特点,并分析其多态性与重要炎症介质诱生的关系。方法收集200例健康献血员外周全血,根据文献通过基因测序对中国北京人群HMGB1启动子区及外显子、外显子和内含子交界区的突变位点进行检测,同时对外周全血体外内毒素（LPs）刺激培养,通过实时定量PCR及酶联免疫吸附试验方法分析,对HMGB1、白介素（IL）～10、肿瘤坏死因子（TNF）-α、IL-6等细胞因子的基因表达和蛋白质分泌水平进行检测,并与HMGB1多态性的相关关系进行分析。结果中国北京地区人群HMGB1存在四种多态性：即rs1412125、rs2249825、rs3742305、rs41376448。在LPS体外刺激后仅rs2249825多态性与HMGB1诱生水平相关,P〈0．05,但基因水平差异无统计学意义,P〉0．05;而其他三种多态性在HMGB1、IL-10、TNF-α、IL-6蛋白质及基因水平均无统计学的意义,均P〉0．05。结论中国北京人群HMGB1的基因有四种多态性,LPS刺激后HMGB1的诱生水平与rs2249825具有相关性,它可能影响HMGB1蛋白质水平的表达。     

Shares in single nucleotide polymorphisms

The announcement of a consortium between the public and private sectors to produce a public single nucleotide polymorphism (SNP) map of the human genome is a unique development which acknowledges the need for research tools to be widely available. The human genome project has been characterised by public-private tensions over information access and ownership. This new initiative demonstrates the scope for collaboration between the interests of the two sectors that are very much in the public interest.     

A novel HLA-Cw*04 allele, Cw*04010103, identified by genomic full length cloning and sequencing

A novel human leukocyte antigen-Cw*04 allele, Cw*04010103, was identified by genomic full length cloning and sequencing from a male Chinese donor. It differs from the closest related allele Cw*04010101 by one nucleotide exchange at nt 1111 (G>A) in intron 3.     

Genetic, epigenetic and environmental impact on sex differences in social behavior

The field of behavioral neuroendocrinology has generated thousands of studies that indicate differences in brain structure and reactivity to gonadal steroids that produce sex-specific patterns of social behavior. However, rapidly emerging evidence shows that genetic polymorphisms and resulting differences in the expression of neuroactive peptides and receptors as well as early-life experience and epigenetic changes are important modifiers of social behavior. Furthermore, due to its inherent complexity, the neurochemical mechanisms underlying sex differences in social behavior are usually studied in a tightly regulated laboratory setting rather than in complex environments. Importantly, specific hormones may elicit a range of different behaviors depending on the cues present in these environments. For example, individuals exposed to a psychosocial stressor may respond differently to the effects of a gonadal steroid than those not exposed to chronic stress. The objective of this review is not to re-examine the activational effects of hormones on sex differences in social behavior but rather to consider how genetic and environmental factors modify the effects of hormones on behavior. We will focus on estrogen and its receptors but consideration is also given to the role of androgens. Furthermore, we have limited our discussions to the importance of oxytocin and vasopressin as targets of gonadal steroids and how these effects are modified by genetic and experiential situations. Taken together, the data clearly underscore the need to expand research initiatives to consider gene-environment interactions for better understanding of the neurobiology of sex differences in social behavior.