Weight gain associated with the -759C/T polymorphism of the 5HT2C receptor and olanzapine.

BACKGROUND: Weight gain from atypical antipsychotic use has become a significant problem. Recent reports have liked the -759 polymorphism of the 5HT2C receptor and obesity as well as weight gain from chlorpromazine, risperidone, and clozapine. AIM: To determine associations between weight gain during olanzapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. METHODS: This study included 42 acutely ill patients with schizophrenia (DSM-IV). Weekly assessments included Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a fixed dose (7.5-20 mg/day) for 2-6 weeks. A 24 hr plasma level was obtained at the endpoint visit. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor. RESULTS: A chi-square analysis was conducted comparing the distribution of T and C alleles in subjects grouped as gaining more or less than 5, 7, and 10% of their baseline weight during treatment with olanzapine. A threshold of 10% was found to be significant. The distribution of T alleles was higher in subjects not gaining 10% of more of their body weight compared who did gain significant weight (11/27 (40.7%) vs. 0/15 (100%), chi2 = 11.805, P = 0.0035). CONCLUSIONS: Subjects with a T allele of the 5HT2C receptor -759C/T polymorphism may have a lower incidence of weight gain from olanzapine over a 6 week period compared to those with the C allele. These results need to be replicated.     

Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism.

Weight gain has been documented as a significant adverse effect associated with many of the atypical antipsychotic medications. Several recent reports have linked a -759C/T polymorphism of the 5HT2C receptor gene and obesity as well as chlorpromazine, risperidone, and clozapine induced to weight gain. This aim was to determine the association between changes in body mass index (BMI) during clozapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. This study included 41 patients with treatment-refractory schizophrenia (DSM-IV) who were followed prospectively during treatment with clozapine. Weight and height measurements were obtained prior to starting clozapine and after 6-months of treatment. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor gene. A chi(2) analysis comparing whether or not the subjects carried a -759T allele in subjects grouped as having an increase of more or less than 7% of their baseline BMI during treatment with clozapine found that the presence of the -759T allele was significantly higher in subjects with less than or equal to a 7% increase in baseline BMI compared to those with a greater than 7% increase in BMI. A multiple linear regression analysis showed that both baseline BMI and the presence or absence of the -759T allele had significant effects on 6-month BMI. The T allele may have a protective function in preventing significant weight gain from clozapine. Subjects without the -759T variant allele were at a greater risk for weight gain from clozapine over 6-months compared to those with the -759T allele.     

Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals

Weight gain is a major side effect of treatment with clozapine and other antipsychotics. Recent studies suggest an important role of the serotonin type 2C receptor gene (5-HT2CR) in antipsychotic-induced weight gain. However, investigations pertaining to a possible association between a -759C/T polymorphism (C allele) of the 5-HT2CR and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results. We investigated the -759C/T polymorphism of the 5-HT2CR in relation to clozapine-induced change in body mass index (BMI) (kg/m) in 97 German patients with schizophrenia and found no association between the -759C allele and weight gain after 12 weeks of clozapine treatment. In addition, confounding effects of initial BMI, age, sex and duration of illness on change in BMI could not be detected by multiple linear regression analysis. Our data do not support an involvement of the -759C/T polymorphism of the 5-HT2CR in clozapine-induced weight gain in German patients with schizophrenia. Further pharmacogenetic studies pertaining to antipsychotic-induced weight gain are warranted.     

自杀未遂与5-羟色胺2A受体基因的关联分析

目的 探讨5-羟色胺（5-HT）2A受体基因A-1438G和T102C两种多态性与自杀未遂之间的关系。方法 以149例自杀未遂者为研究对象。190名正常人为对照,采用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法,分析5-HT2A受体基因A-1438G和T102C多态性。结果 PCR-RFLP分析发现,男性自杀未遂与5-HT2A受体基因A-1438G多态性的基因型GG关联。结论 5-HT2A受体基因A-1438G多态性可能与男性的自杀易感性相关。     

抗精神病药物引发的体重增加与HTR2C基因-759C/T 多态性关联的Meta分析

目的 探讨抗精神病药物在治疗精神分裂症患者过程中出现的体重增加与5羟色胺2C受体（HTR2C）基因启动子区-759C/ T（rs3813929）单核苷酸多态性的关系。方法 在Pubmed、 Springer、China biology medicine disc（CBM）、谷歌学术、万方数据库等检索1990~2017年精神分裂症患者中有关HTR2C-759C/T 基因多态性与抗精神病药物诱导的体重增加关联性研究的文献,对-759C/T 位点（CT+TT）/CC,（CT+CC）/TT基因型进行Meta分析。用RevMan version 5.3计算OR值及95%可信区间,并按人种因素作亚组分析。结果 共有20篇文献符合纳入标准,经Meta分析发现HTR2C-759T与抗精神病药物引发的体重增加呈显著负相关[（CT+TT）/ CC OR=0.42,95%CI（0.26~0.66）,P=0.0002]。亚组分析中,高加索人群和东亚人群含HTR2C-759T患者的体重增加占比人数显著低于CC基因型患者（高加索人群OR=0.48,95%CI（0.26~0.88）,P=0.020,东亚人群OR=0.34,95%CI（0.17~0.69）,P=0.002）。HTR2C-759C 与抗精神病药物引发的体重增加有正相关趋势[（CT+CC）/TT OR=2.29,95% CI（1.00~5.23）,P=0.05]。亚组分析中高加索人群[OR=2.58,95% CI（0.61~10.94）,P=0.200]和东亚人群（OR=2.13,95%CI（0.78~5.86）,P=0.14）结论一致,差异无统计学意义（P＞0.05）。结论 HTR2C 基因启动子-759C/T单核苷酸多态性与抗精神病药物导致的患者体重增加相关联,携带HTR2C-759T可能是限制体重增加的保护因子。     

A family-based study of the Cys23Ser 5HT2C serotonin receptor polymorphism in schizophrenia

The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore been postulated to play a role in mediating negative symptoms and neuroleptic response in schizophrenia. In the current study, the Cys23Ser 5HT2C serotonin receptor polymorphism was examined for linkage to schizophrenia by genotyping 207 nuclear families consisting of both parents and schizophrenic child and using the transmission disequilibrium test to examine possible preferential transmission of these alleles from 68 heterozygous mothers to their ill child. No evidence was obtained for preferential transmission of the Cys23Ser 5HT2C alleles in schizophrenia in either of the two main ethnic groups examined (German and Palestinian Arab) or in the combined cohort (TDT chi-square = 0.00, NS).     

A family‐based study of the Cys23Ser 5HT2C serotonin receptor polymorphism in schizophrenia

The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore been postulated to play a role in mediating negative symptoms and neuroleptic response in schizophrenia. In the current study, the Cys23Ser 5HT2C serotonin receptor polymorphism was examined for linkage to schizophrenia by genotyping 207 nuclear families consisting of both parents and schizophrenic child and using the transmission disequilibrium test to examine possible preferential transmission of these alleles from 68 heterozygous mothers to their ill child. No evidence was obtained for preferential transmission of the Cys23Ser 5HT2C alleles in schizophrenia in either of the two main ethnic groups examined (German and Palestinian Arab) or in the combined cohort (TDT chi‐square = 0.00, NS). © 2001 Wiley‐Liss, Inc.     

多巴胺受体D2型基因启动区多态性与精神分裂症关联研究

目的探讨湖北武汉地区汉族人群中多巴胺受体D2型基因(dopamine receptor D2, DRD2)启动区-141位点胞嘧啶插入/缺失多态性与精神分裂症的关联关系.方法应用聚合酶链反应-限制性片段长度多态性方法,对120例精神分裂症患者、100名健康对照者进行基因分型.对精神分裂症患者的 DRD2 -141位点胞嘧啶插入/缺失多态性进行了相关分析.结果 DRD2型基因启动区-141位点的等位基因、基因型频率在精神分裂症组与对照组之间的分布差异有统计学意义(P<0.05).在精神分裂症组中,-141C缺失的等位基因频率为0.11,对照组为0.18(比值比为0.55,95%可信区间为0.30～0.96,P <0.05).结论 -141位点胞嘧啶插入/缺失多态性非独立性地对精神分裂症与 DRD2基因的相关性产生修饰作用.-141位点胞嘧啶缺失可能是湖北武汉汉族精神分裂症患者的保护因素之一.     

传统抗精神病药物所致迟发性运动障碍的药理遗传学初步研究

目的：进一步探讨多巴胺D2、D3受体（dopamine D2,D3 receptor,DRD2,DRD3)功能基因多态性与迟发性运动障碍(tardive dyskinesia,TD）的相关性及各候选基因，同时包括五羟色胺2C受体（5－hydroxytryptamine 2C receptor,HTR2C）和锰超氧化物歧化酶（manganese superoxide dismutase,MnSOD）基因的相互作用对TD发生的影响。方法：使用异常不自主运动量表（abnormal involuntary movement scale,AIMS)评定精神分裂症（schizophrenia,CSH)患者有无TD及其严重程度，并采用简明精神病评定量表评定患者精神症状；应用聚合酶链反应－限制性片段长度多态性技术分析TD组和非TD组各候选基因等位基因和（或）基因型分布频率及其结合分布频率，并分析对AIMS总分值的影响。结果：各候选基因在SCH患者组以及TD和非TD组基因型分布均符合Hardy-Weinberg平衡定律；TD组HTR2C基因－697C（突变型）等位基因频率高于非TD组，差异有显著性（P＜0．05）；DRD2基因Taq I A1/A2、DRD3基因Ser9Gly和MnSOD基因Ala-9Val等位基因频率和基因型分布在TD组与非TD组之间差异均无显著性（P＞0．05）；仅DRD3突变型（Gly）和MnSOD野生型（Val）结合分布频率高于其它结合型，差异有显著性（P＜0．05）；但上述各候选基因不同等位基因和（或）基因型亚组间的临床学资料和AIMS总分值（TD值）差异均无显著性（P＞0．05）。结论：HTR2C基因启动区－697G→C单碱基置换可能是中国汉族男性SCH患者TD发生的易感因素；而SCH患者若同时携带DRD3基因9Gly突变型和MnSOD基因－9Val野生型等位基因可能增加了TD的易感性。     

精神分裂症与六种候选功能基因的关联研究

目的：探讨多巴胺D2受体基因（dopamine D2 receptor,DRD2)、多巴胺D4受体基因（DRD4）、5－羟色胺2A受体基因（5－hydroxytryptamine 2A receptor,5-HT2A),5-羟色胺6受体基因（5－HT6)、儿茶酚胺氧位甲基转移酶基因（catechol-O-methyltransferase,COMT)和多巴胺转运体基因（dopamine transferase,DAT1)多态性与精神分裂症的关系。方法：应用基因扩增片段长度多态和基因扩增的限制性片段长度多态技术，对中国汉族人群中67例精神分裂症患者与上述6种候选功能和基因扩增的限制性片段长度多态技术，对中国汉族人群中67例精神分裂症患者与上述6种候选功能基因进行遗传关联分析。结果：（1）DRD2、5－HT2A、5－HT6和KCOMT的基因型和等位基因频率在患者组和对照组中差异无显著性（P＞0．05）。（2）DRD4基因中6次重复序列等位基因、DAT1基因中480bp等位基因和480／520基因型在两组中差异有显著性，Z分别为2．03、2．05和2．05；P均小于0．05。（3）经关联分析后，仅DAT1基因的480bp等位基因的比值比为0．441，95％可信区间为0．202－0．963，并有显著性意义（Z＝2．05，P＜0．05），而DAT1的480／520基因型和DRD4和6次重复序列等位基因的比值比分别为0．128和0．123，但Z均小于1．96，无显著性意义（P＞0．05）。因此，6个功能基因中仅DAT1的480bp等位基因与精神分裂症呈负关联。结论：中国汉族人群中DAT1基因的480bp等位基因与精神分裂症间存在负关联，支持精神分裂症的多巴胺假说。     

No association or linkage between the 5-HT2a/T102C polymorphism and schizophrenia in Irish families

Recent findings of an association between schizophrenia and a T102C polymorphism at the 5-HT^2a receptor gene (particularly with genotype 1-2 and 2-2 and allele 2) prompted us to investigate this marker in familial Irish schizophrenic patients, their relatives, and ethnically matched unrelated controls; 247 probands and 249 controls were included in this study. In contrast to some studies, we found no evidence of significant differences either in the frequency of the genotypes 1-2 and 2-2 or allele 2 between the schizophrenic patients and the controls. A transmission disequilibrium test, run on the full set of 265 families yielded no evidence to support linkage disequilibrium. Linkage analysis with both parametric and non-parametric methods yielded strongly negative results. Our findings are consistent with other recent association studies which argue against the involvement of the 5-HT_2a/T102C polymorphism in predisposition to schizophrenia. The positive findings reported to date might have occurred by chance or the apparent conflict may be due to genetic heterogeneity between samples. Am. J. Med. Genet. 74:370–373, 1997. © 1997 Wiley-Liss, Inc.     

Association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes

OBJECTIVE: To study the association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes in Chinese population. METHODS: PCR-restriction fragment length polymorphism was used to determine the Pro12Ala and C1431T polymorphisms in 207 patients with type 2 diabetes and 101 non-diabetic control subjects. RESULTS: (1) In non-diabetic control population, the Ala allele frequency was 0.064, the T1431 allele frequency was 0.252. Haplotype analysis showed that the Pro12Ala and C1431T polymorphisms were in linkage disequilibrium (Do=0.63, r(2)=0.074), which constituted three major haplotypes Pro-C, Pro-T and Ala-T. (2) There were no significant differences of the distribution frequencies of the Pro12Ala and C1431T polymorphism and their haplotypes between the type 2 diabetes mellitus group and non-diabetic control group (P > 0.05). (3) The Pro12Ala polymorphism was associated with blood pressure and lipidemia in diabetic patients. The Ala allele significantly decreased the diastolic blood pressure of non-obese diabetic patients (P < 0.05), but it did not benefit to the obese diabetic patients for the lipidemia (P < 0.05). The C1431T polymorphism was associated with overweight and obesity in diabetic patients. The T1431 allele frequency in the body mass index >/= 25 layer was significantly higher than that in the body mass index < 25 layer (P < 0.05). CONCLUSION: The Pro12Ala and C1431T polymorphisms of the PPAR gamma2 gene might not be a major etiological factor for type 2 diabetes; the C1431T polymorphism was associated with overweight or obesity in diabetic patients.     

Lack of association of serotonin‐2A receptor gene polymorphism (T102C) with suicidal ideation and suicide

Serotonergic dysfunction has been implicated in the pathophysiology of affective disorders and suicidality. Especially the density of the 5‐HT2A receptor was claimed as being increased in suicidality, proposed as an adaptive upregulation due to reduced serotonergic transmission. Recent studies have shown an association of allele C of the 5‐HT2A‐T102C polymorphism with suicidal ideation in patients with major depression. The purpose of this study was to test whether this proposed marker indicates susceptibility not only to suicidal ideation in depressed patients but also to suicidality as a syndrome. We investigated the 5‐HT2A‐T102C polymorphism in 131 suicide victims with unknown underlying psychiatric diagnoses, 84 patients with major depression with or without suicidal ideation, and 125 healthy controls. We were unable to find any association of genotype or allele frequencies to major depression, suicidal ideation, or suicide as a syndrome. Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831–835, 2000. © 2000 Wiley‐Liss, Inc.     

基质金属蛋白酶9基因-1562C/T多态性与新疆维吾尔族心肌梗死的相关性研究

目的 探讨新疆维吾尔族人群基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)基因启动子区-1562C/T多态性与心肌梗死(myocardialinfarction,MI)发病的相关性.方法 选择经皮冠状动脉造影检查确诊的维吾尔族心肌梗死患者347例(MI组),以同期冠脉造影阴性、排除冠心病诊断的403例维吾尔族患者为对照组.采用聚合酶链反应-限制性片段长度多态性方法对所有纳入对象MMP9基因-1562C/T多态性进行分析,比较两组间MMP9基因多态性频率分布的差异,并结合造影情况,探讨MMP9基因多态性与MI发病及冠脉狭窄程度的关系.结果 MI组CT+TT基因型频率(27.67%)明显高于对照组(14.14%),两组差异具有统计学意义(χ2=20.99,P＜0.01),T等位基因频率在MI组和对照组分别为15.71%、7.56%(χ2=24.57,P＜0.01).Logistic回归分析显示,携带-1562T等位基因的个体发生MI的风险大约升高2倍(OR=2.009,95%CI:1.250～3.230);携带T等位基因合并糖尿病的个体发生MI的风险明显升高(OR=3.714,95%CI:1.299～10.773).MMP9基因-1562C/T多态性分布与MI冠脉狭窄程度差异无统计学意义.结论 MMP9基因-1562C/T多态性可能与新疆维吾尔族人群MI茇病具有相关性;-1562T等位基因可能是MI遗传易感性的基因标记之一;-1562T等位基因与糖尿病在MI发生中具有协同作用.MMP9基因-1562C/T多态性与MI冠脉狭窄程度无关.

Abstract：

Objective To investigate the association between matrix metalloproteinase 9 gene (MMP9)- 1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.Methods A total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed. Results The results showed that the frequency of CT and TT genotypes in patients with MI (27. 67%) was significantly higher than that in controls (14. 14%). The frequencies of the - 1562T allele were 15. 71% and 7. 56% in the MI group and the control group respectively (2 = 24.57, P＜0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2. 009, 95%CI: 1. 250-3. 230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3. 714, 95% CI: 1. 299-10. 773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (χ2 =0. 491, P=0. 782). Conclusion The - 1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI.The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.     

Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder

There is evidence indicating that density of 5-HT2A receptors is altered in brain regions of depressed suicide victims and in platelets of suicidal subjects with major depression or schizophrenia. Recent studies have also shown an association between the allele C of 102T/C polymorphism in the 5-HT2A receptor gene and schizophrenia. The present investigation tested the hypothesis that the observed changes in 5-HT2A receptor density in platelets of patients with major depression are a trait rather than state phenomenon and are associated with the 102 C allele in 5-HT2A receptor gene in a sample of 120 patients with major depression and a group of 131 control subjects comparable with respect to age, sex, and ethnic background. The allele and genotype frequencies of 102T/C polymorphism in 5-HT2A receptor gene were compared between patients and control subjects and between suicidal and non-suicidal patient groups. The major finding of this study was a significant association between the 102 C allele in 5-HT2A receptor gene and major depression, chi(2) = 4.5, df = 1, P = 0.03, particularly in patients with suicidal ideation, chi(2) = 8.5, df = 1, P < 0.005. Furthermore, we found that patients with a 102 C/C genotype had a significantly higher mean HAMD item 3 score (indication of suicidal ideation) than T/C or T/T genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:56-60, 2000.     

肿瘤坏死因子α基因启动子区域-1031T/C多态与不稳定性心绞痛的相关性

目的 研究肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)基因启动子区域-1031T/C多态与汉族不稳定性心绞痛的相关性.方法 采用MALDI-TOF质谱检测方法,在299例不稳定性心绞痛患者和202名健康对照者中,对TNF-α基因启动子区域的T-1031C多态进行基因分型,并采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)法测定其血清浓度.结果 -1031T/C多态的基因型分布及其等位基因频率在两组间相比差异均无统计学意义(P>0.05).但在男性不稳定性心绞痛患者中,其CC、TC和TT基因型分布与对照组相比有统计学意义(P=0.032),男性CC+TC携带者,不稳定性心绞痛的发病危险是TT携带者的1.66倍(95%CI:1.040～2.659).其等位基因频率在两亚组间相比差异无统计学意义(P>0.05).不稳定性心绞痛组的血清TNF-α浓度明显高于对照组(P=0.028,尤其男性亚组P=0.013),TC基因型的血清TNF-α浓度高于其他基因型,但差异无统计学意义(P>0.05).结论 TNF-α基因启动子区域的-1031T/C多态可能与男性不稳定性心绞痛的发生相关,尤其是男性C等位基因携带者.     

Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population.     

PPARY2基因Pro12Ala和C1431T多态性及其单倍型与2型糖尿病和肥胖的相关性研究

目的 研究过氧化物体增殖活化受体γ2(peroxisome proliferator activated receptorγ2,PPARγ2)基因Pro12Ala和C1431T多态性及其单倍型与汉族人2型糖尿病、肥胖的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对207例2型糖尿病患者和101名非糖尿病对照者进行PPARγ2基因Pro12Ala和C1431T多态性研究.结果 (1)在非糖尿病对照人群中Aal 12等位基因频率是0.064,T1431等位基因频率是0.252.单倍型分析显示Pro12Ala和C1431T两个位点连锁不平衡(D'=0.63,r2=0.074),组成了3种常见单倍型Pro-C、Pro-T和Ala-T.(2)Pro12Ala和C1431T多态性分布及其单倍型分布频率在2型糖尿病组与对照组组间差异均无统计学意义(P>0.05).(3)Pro12Ala变异与糖尿病患者的血压、血脂相关,地等位基因降低非肥胖糖尿病患者的舒张压(P<0.05),而对肥胖糖尿病患者的血脂水平无保护作用(P<0.05);C1431T多态性与糖尿病患者的超重和肥胖相关,超重和肥胖的糖尿病者T等位基因频率相对较高(P<0.05).结论 Pro12Ala和C1431T多态性可能在汉族人糖尿病发病中不是起主要作用;C1431T多态性与糖尿病患者的超重和肥胖相关.     

The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients.

Several lines of evidence suggest that genetic factors constitute an important determinant of suicidal behavior. A significant association between the 5-HT(2A)-C allele and suicidality has recently been reported. The aim of this study was to investigate whether the proposed association between 5-HT(2A)-102T/C polymorphism and suicidality could be replicated in a larger and independent sample of Spanish patients with major depression. The 102T/C polymorphism of the 5-HT(2A) receptor gene was analyzed in 159 patients with major depression (DSM-IV criteria) and 164 unrelated and healthy controls using a case control design. All individuals were subjects of Spanish origin. Significant differences in allele (chi-square = 4.13, df = 1, P = 0.04) and genotype (chi-square = 6.19, df = 2, P = 0.04) distributions were found between non-suicide attempters and suicide attempters. Moreover, those patients carrying 5-HT(2A)-C allele had more than five times the risk for attempting suicide than noncarriers (OR = 5.50, 95% CI = 1.18-35.20, P = 0.01). Our results replicate the proposed association between 5HT(2A)-C allele and suicidality in major depression. Moreover, no overall associations are detected when patients with major depression and controls are compared for 102T/C frequencies, suggesting that the increased risk for suicidality conferred by 5-HT(2A)-C allele is primarily associated with suicidal behavior and not with the diagnosis of major depression itself.     

白细胞介素6受体基因单核苷酸多态性与2型糖尿病的关联性

目的探讨甘肃地区汉族人中白细胞介素6受体基因（interleukin 6 receptor gene，IL6R）启动子-183（G→A）和第9外显子D358A的变异与2型糖尿病（type 2 diabetes mellitus，T2DM）的关联。方法随机选取无亲缘关系甘肃地区汉族人183名，其中T2DM患者87例、正常对照96名，应用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism，PCR-RFLP）方法进行-183（G→A）和D358A变异的检测。结果正常对照组D358A的3种基因型频率和等位基因频率分别为AA31．2％、AC41．7％、CC27．1％、A52．1％、C47．9％，2型糖尿病组相应为AA44．8％、AC41．4％、CC13．8％、A65．5％、C34．5％，正常对照组CC基因型频率和C等位基因频率高于2型糖尿病组（χ^2=4．900，P〈0．05；χ^2=6．784，P〈0．01）。-183（G→A）3种基因型频率和等位基因频率差异无统计学意义。结论提示该基因D358A多态可能与中国人2型糖尿病关联。