Association of genetic polymorphisms with personality profile in individuals without psychiatric disorders

Objective

Population-based twin studies demonstrate that approximately 40–50% of the variability in personality dimensions results from genetic factors.This study assessed selected polymorphisms in the COMT Val158Met, MAOA 3′VNTR, 5HTTLPR, 102T/C 5-HT2A, DAT 3′VNTR and DRD2 exon 8 genes and evaluated their association with personality profiles, anxiety levels, and depressiveness in healthy subjects.

Methods

This study included 406 unrelated (mean age 38.51 years), mentally and somatically healthy Caucasian subjects of Polish origin. The prevalence of the gene variants mentioned above and their association with personality profiles, anxiety levels, and depressiveness was assessed using the Temperament and Character Inventory, NEO Five-Factor Inventory, Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory.

Results

The effects of the 5HTTLPR gene on the s/s genotype and empathy (C2) were lowest in the entire group. The effects of gender, age and the HT2A gene for the T/T genotype and attachment (RD3) were highest in women.The effects of gender, age and the DAT gene on the 9/9 DAT genotype, compassion (C4) and cooperativeness (C) were lowest in women. The effects of gender, age and the COMT gene on the Met/Met genotype and neuroticism (NEU) NEO-FFI were also lowest in women.

Conclusions

Our results suggest considerable influence of individual genes on the formation of personality traits.     

Association between MspI polymorphism of the APO AI gene and Type 2 diabetes mellitus.

AIMS: Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain. METHODS: A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all < or = 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped. RESULTS: Those subjects with the mutated AA genotype of the MspI polymorphism (-75 G-->A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02-3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3-39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4-9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance. CONCLUSIONS: Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A-I/C-III/A-IV cluster, seems to be a risk factor for Type 2 diabetes mellitus.     

张家口地区健康人群CYP1A1基因多态性

目的 探讨张家口地区健康人群CYP1A1基因MspI和Ile/Val的多态性.方法 采用等位基因特异性扩增和PCR-限制性片段长度多态性(RFLP)技术,分析360例张家口地区健康成人的CYP1A1基因3′端限制性内切酶MspI位点和Exon7位点的3种基因型的分布规律.结果 张家口健康人群MspI基因型m1m1占35.8%,基因型m1m2占50.2%,基因型m2m2占14.0%,等位基因m1m2分别为60.9%,39.1%.Ile/Val多态性,其Ile及Val等位基因的频率分别为68.5%,31.5%.Ile/Ile,Ile/ Val,Val/Val基因型分布频率分别为44.4%,48.1%,7.5%.结论 张家口地区健康人群CYP1A1基因存在MspI和Ile/Val的多态性.     

Association of CYP1A1 MspI polymorphism in the esophageal cancer risk: a meta-analysis in the Chinese population

Background

Although many epidemiologic studies have investigated the CYP1A1 MspI gene polymorphisms and their associations with esophageal cancer (EC), definite conclusions cannot be drawn. To clarify the effects of CYP1A1 MspI polymorphisms on the risk of EC, a meta-analysis was performed in Chinese population.

Methods

Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations.

Results

A total of 13 studies including 1,519 EC cases and 1,962 controls were involved in this meta-analysis. Overall, significant association was found between CYP1A1 MspI polymorphism and EC risk when all studies in the Chinese population pooled into this meta-analysis (C vs. T: OR = 1.25, 95% CI = 1.04 to 1.51; CC + CT vs. TT: OR = 1.35, 95% CI = 1.06 to 1.72; CC vs. TT + CT: OR = 1.35, 95% CI = 1.03 to 1.76). When we performed stratified analyses by geographical locations, histopathology type, and source of control, significantly increased risks were found in North China (C vs. T: OR = 1.38, 95% CI = 1.12 to 1.70; CC vs. TT: OR = 1.72, 95% CI = 1.16 to 2.56; CC + CT vs. TT: OR = 1.52, 95% CI = 1.14 to 2.02; CC vs. TT + CT: OR = 1.55, 95% CI = 1.17 to 2.06), in the population-based studies (C vs. T: OR = 1.22, 95% CI = 1.05 to 1.42; CC vs. TT: OR = 1.38, 95% CI = 1.02 to 1.88; CC + CT vs. TT: OR = 1.36, 95% CI = 1.10 to 1.69; CC vs. TT + CT: OR = 1.43, 95% CI = 1.13 to 1.81) and ESCC (C vs. T: OR = 1.17, 95% CI = 1.04 to 1.32; CC + CT vs. TT: OR = 1.28, 95% CI = 1.08 to 1.52).

Conclusions

This meta-analysis provides the evidence that CYP1A1 MspI polymorphism may contribute to the EC development in the Chinese population.     

DNA (Cytosine-C5) methyltransferase inhibition by oligodeoxyribonucleotides containing 2-(1H)-pyrimidinone (zebularine aglycon) at the enzymatic target site

Aberrant cytosine methylation in promoter regions leads to gene silencing associated with cancer progression. A number of DNA methyltransferase inhibitors are known to reactivate silenced genes; including 5-azacytidine and 2-(1H)-pyrimidinone riboside (zebularine). Zebularine is a more stable, less cytotoxic inhibitor compared to 5-azacytidine. To determine the mechanistic basis for this difference, we carried out a detailed comparisons of the interaction between purified DNA methyltransferases and oligodeoxyribonucleotides (ODNs) containing either 5-azacytosine or 2-(1H)-pyrimidinone in place of the cytosine targeted for methylation. When incorporated into small ODNs, the rate of C5 DNA methyltransferase inhibition by both nucleosides is essentially identical. However, the stability and reversibility of the enzyme complex in the absence and presence of cofactor differs. 5-Azacytosine ODNs form complexes with C5 DNA methyltransferases that are irreversible when the 5-azacytosine ring is intact. ODNs containing 2-(1H)-pyrimidinone at the enzymatic target site are competitive inhibitors of both prokaryotic and mammalian DNA C5 methyltransferases. We determined that the ternary complexes between the enzymes, 2-(1H)-pyrimidinone inhibitor, and the cofactor S-adenosyl methionine are maintained through the formation of a reversible covalent interaction. The differing stability and reversibility of the covalent bonds may partially account for the observed differences in cytotoxicity between zebularine and 5-azacytidine inhibitors.     

Concurrent expression of aryl hydrocarbon receptor and CYP1A1 but not CYP1A1 MspI polymorphism is correlated with gastric cancers raised in Dalian, China

The frequency of cancer-associated m2m2- (C-) genotype of CYP1A1 and the factors contributing to the increased CYP1A1 expression in gastric cancers (GCs) are largely unknown. To address theses issues, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to elucidate the MspI polymorphism in 60 GC cases and 57 normal donor samples. The frequencies of m1m1-, m1m2- and m2m2-genotype were 43.3, 45 and 11.7% among GC patients and 45.6, 49.1 and 5.3% among the normal donors respectively, demonstrating no significant difference of them between cancer and control groups (χ²=0.343, P=0.558). The correlation of Aryl hydrocarbon receptor (AhR) with the frequent CYP1A1 expression in stepwise gastrocarcinogenesis was determined by RT-PCR, immunohistochemical staining (IHC) and Western blotting, using GC samples as well as their pre-malignant and non-cancerous counterparts. RT-PCR revealed that the AhR detection rates were 100, 94.12 and 85.17% in GC, pre-malignant and non-cancerous mucosa (P>0.05) respectively but the level of AhR expression in GCs was much higher than that of non-cancerous tissues. IHC showed that the frequencies of AhR detection were 94.87% (37/39) in GCs, 94.12% (16/17) in pre-malignant lesions and 50% (3/6) in non-cancerous mucosa, revealing significant difference in frequencies of AhR detection and levels of AhR expression between GC or pre-malignant group and non-cancerous one (P<0.05). The frequency of AhR nucleus translocation was significantly high in GCs (94.87%; 37/39) than that in pre-malignant (70.59%; 12/17) and especially in non-cancerous group (16.67%; 1/6). Co-existence of AhR nuclear translocation and CYP1A1 expressions were found in 82.70% (43/52) of GCs (r_s=0.437, P<0.01). Our results suggest (1) that CYP1A1 MspI polymorphism may not contribute to the high gastric cancer risk in Dalian region and (2) that enhanced AhR expression and especially its nuclear translocation may be a favorable factor for GC formation presumably via up-regulating CYP1A1 expression.     

国人载脂蛋白A1基因多态性与血脂水平及冠心病的关系

为探讨载脂蛋白A1基因 - 75bp +83bp位点多态性与血脂水平及冠心病发生之间的关系 ,采用生物化学方法分别测量经冠状动脉造影证实的 92例冠心病患者及 4 5例正常人空腹血脂水平 ,应用聚合酶链反应对载脂蛋白A1基因DNA 4 33bp的 5’末端片段进行限制性片段长度多态性分析。结果发现 ,冠心病组甘油三酯、总胆固醇、低密度脂蛋白、载脂蛋白B及脂蛋白 (a)水平均高于对照组 (均P <0 .0 5 ) ,而高密度脂蛋白 (P <0 .0 0 5 )与载脂蛋白A1 (P <0 .0 5 )水平则低于对照组 ;冠心病组较对照组M1 -及M2 -基因型频率明显为低 (P <0 .0 0 5 ,P <0 .0 5 ) ;与M1 + +相比 ,M1 +- - -者血中高密度脂蛋白及载脂蛋白A1水平分别升高 1 8.0 9%和 1 5 .6 8% ,而M2 +- - -者血中高密度脂蛋白及载脂蛋白A1水平较M2 + +分别升高 6 .1 9%和 8.6 5 %。以上结果表明 ,载脂蛋白A1基因- 75bp位点G被A取代及 +83bp位点C被T取代或G被A取代后个体血载脂蛋白A1及高密度脂蛋白水平升高 ;这些碱基变化可能会导致个体发生冠心病的危险性降低     

昆明汉族急性脑梗死患者vWF基因多态性研究

目的阐明vWF基因19内含子MspI多态性在昆明地区人群中的分布;探讨vWF基因19内含子MspI多态性与急性缺血性脑梗死的关系。方法收集119例急性缺血性脑梗死患者(脑梗死组)和117名昆明地区健康人(对照组),应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析vWF基因19内含子MspI多态性。结果昆明地区汉族人群中vWF基因19内含子M+/M+、M+/M-和M-/M-基因型频率分别为0.034、0.470和0.496;M+和M-等位基因频率分别为0.269和0.731。脑梗死组中M+/M+、M+/M-和M-/M-基因型频率分别为0.059、0.286和0.655,M+等位基因和M-等位基因频率分别为0.202和0.798,其M+/M-基因型频率低于对照组,M-/M-基因型频率高于对照组。2组基因频率分布差异有统计学意义(P<0.05)。结论昆明地区汉族人群中vWF基因19内含子MspⅠ酶切位点各基因型的分布与文献报道中的高加索人群差异较大,与中国地区其他民族人群也不尽相同。急性脑梗死的发生可能与vWF基因19内含子MspI多态性有关。     

Cytochrome P450IA1 polymorphisms along with PM(10) exposure contribute to the risk of birth weight reduction

We explored the effects of particulate matter <10 μm (PM₁₀) exposure along with CYP1A1 polymorphisms of MspI (T6235C) and NcoI (Ile462Val) on reduced birth weight (BW). A prospective cohort study was done with women who delivered from 2001 to 2004 at Ewha Womans University Hospital, Seoul, Korea. We compared the estimated least squares means of BW in the generalized linear model, after adjusting for controlling factors. High PM₁₀ exposure at the 90th percentile level and above during the 1st trimester conferred a significant risk for reduced BW, compared with low PM₁₀ exposure below the 90th percentile level. The effect of high PM₁₀ exposure during the 1st trimester of pregnancy compared with low PM₁₀ exposure was greater for women with MspI TC/CC and NcoI IleVal/ValVal genotypes than for those with MspI TT and NcoI IleIle genotypes. In conclusion, high PM₁₀ exposure during the 1st trimester increased the risk for reduced BW in concert with MspI TC/CC and NcoI IleVal/ValVal genotypes in Korean women.