维生素D受体基因多态性与骨关节炎关系的Meta分析

背景:维生素D受体与骨关节炎存在密切联系,而维生素D受体基因多态性被认为能够调控维生素D受体,进而影响骨关节炎的发生,但现有的研究仍存在争议。目的:确认维生素D受体基因多态性与骨关节炎的关系。方法:系统检索PubMed、Web of Science、EMbase、Cochrane Library、中国生物医学文献数据库、中国学术期刊全文数据库、万方、维普等数据库,检索时限均为建库截至2019年10月,检索所有提供了骨关节炎患者和非骨关节炎患者维生素D受体基因(ApaI、Bsm I、TaqI和Fok I)多态性数据的病例对照研究,采用Stata 14.0统计软件进行分析。结果与结论:①总共纳入21篇相关研究,共7 109例患者,其中包括骨关节炎患者3 123例,非骨关节炎患者4 006例;②Meta分析显示,欧洲人维生素D受体Bsm I多态性与骨关节炎之间存在相关性[(BB vs. bb:OR=1.677,95%CI(1.051,2.676),P=0.030;BB vs. Bb+bb:OR=1.780,95%CI(1.175,2.697),P=0.007],但只有3篇研究;亚洲人维生素D受体FokI多态性与骨关节炎之间存在相关性[(FF vs. Ff+ff:OR=0.609,95%CI(0.410,0.907),P=0.015],只有3篇研究;维生素D受体TaqI和ApaI多态性与骨关节炎无显著相关性,在排除异质性后结果也无明显相关性;③结果表明,维生素D受体ApaI、Bsm I、TaqI和FokI多态性可能与骨关节炎无明显相关性。     

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

Background

Major depressive disorder (MDD) and bipolar disorder (BPD) have significant genetic predisposition. The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a susceptibility gene for both MDD and BPD. In the current study the genetic effects of rs2230912 (Gln460Arg) and rs1653625 (located in the 3′ untranslated region of the P2RX7 gene) were explored in mood disorders.

Methods

Genotype frequencies were established in 315 patients (195 with MDD and 120 with BPD diagnosis) and in 373 controls. Depression severity was assessed by the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS) and by the self-report Hospital Anxiety and Depression Scale (HADS).

Results

In the case-control analysis we did not find any significant differences between genotype frequencies of either BPD or MDD cases and controls. However, BPD patients carrying at least one rs2230912 G-allele scored higher on both MADRS and HADS-depression scale (nominal p-value was 0.028 and 0.003, respectively). The rs1653625 AA genotype was also associated with higher depression scores in the BPD group (nominal p-value of MADRS: 0.019, HADS-depression: 0.017). After correction for multiple testing, the association between rs2230912 and HADS-depression score remained significant in the BPD group (p<0.006); this genetic effect explained 9% of the variance (partial η²=0.09). In the MDD group we did not find any significant genetic effect.

Limitations

The relatively small number of BPD patients warrants for a replication study.

Conclusions

Our genetic association study supports the association between P2RX7 gene and severity of depressive symptoms in BPD patients.     

Treatment of maternal mood disorder and infant behaviour disturbance in an Australian private mothercraft unit: a follow-up study

Summary Australia has a system of residential parentcraft services which offer brief admissions to mothers experiencing difficulties with infant care and postnatal mood disturbance. Most of these are state-funded public access services. In 1996 a comparable but differentiated service was opened in the private sector. Masada Private Hospital Mother Baby Unit accommodates five mother-infant pairs who are admitted to a five-night structured residential program. Care is provided by a multidisciplinary team comprising a paediatrician, general practitioner, clinical psychologist and specialist nurses. Complex maternal mood disorders as measured on standardised psychometric instruments include depression, anxiety and severe occupational fatigue. Their babies are unsettled, cry for prolonged periods, wake frequently at night and do not sleep well during the day. Many have feeding difficulties. The treatment program comprises both individualised training in infant care and settling strategies and psycho-educational groups offered in a supportive non-judgemental setting. One month post-discharge maternal mood is significantly improved and infant behaviour more manageable compared with functioning on admission.The material was presented at the Marcé Society International Biennial Scientific Meeting in Sydney (Australia) in 2002 (25–27 September 2002).     

Mothers' dopamine receptor polymorphism modulates the relation between infant fussiness and sensitive parenting

We determined whether the combination of the 48‐bp variable number tandem repeat polymorphism of the dopamine (DRD4) gene and infants' (fussy‐difficult) temperament predicted parenting sensitivity. The sample was comprised of 147 mothers and their 6‐month olds. Sensitive parenting was assessed by coding filmed interactions between mothers and infants. Infant temperament was assessed by parents' reports on a standard questionnaire. Moderated regressions models, with maternal education and infants' interactive behavior as controls, were used to test our hypotheses. Results showed no main effects of either temperament or DRD4, though the maternal DRD4 × infant temperament interaction was significant. Probes indicated that parents with a DRD4 7‐repeat allele behaved more sensitively to fussier infants and less sensitively to less fussy infants compared to parents without the 7‐repeat allele. Among those parents, sensitivity did not vary with infant temperament. This pattern of results indicates that mothers are differentially susceptible to infant fussiness, dependent on the presence of the 7‐repeat DRD4 allele. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:149–157, 2010     

Association study between cannabinoid receptor gene (CNR1) and pathogenesis and psychotic symptoms of mood disorders*

Cannabis can induce mood change and sometimes psychotic symptoms in normal persons. In brain, the main active ingredient of cannabis acts via the cannabinoid CB1 receptor (CNR1) which is located on chromosome 6q14‐15. Linkage studies have suggested the presence of a bipolar disorder susceptibility locus on chromosome 6q. In this population based association study, we tested the hypothesis that a microsatellite polymorphism in the promoter region of the CNR1 gene confers susceptibility to mood disorders and psychotic features. We genotyped the CNR1 gene is 154 mood disorder patients and 165 normal controls. The results showed that the triplet repeat polymorphism in the promoter region of the CNR1 gene was not likely to be involved in the pathogenesis or in the psychotic symptoms of mood disorders. © 2001 Wiley‐Liss, Inc.     

小鼠催产素受体基因编码区全长的克隆和真核表达

目的 :为了获得小鼠催产素受体 (mouseoxytocinreceptor,mOTR)基因的全长编码区和构建mOTR的真核表达载体 ,以及在哺乳动物细胞中真核表达mOTR。方法 :采用RT PCR方法 ,获得有相互重叠序列的mOTR的羧基端和氨基端的cDNA片段并分别将其亚克隆入PMD 18 T载体。通过对这 2个片段加入酶切位点、双酶切和相互连接 ,获得全长的编码序列。然后将mOTR的全长的编码序列克隆入真核表达载体pEGFP N3,再用脂质体转染法将pEGFP N3 mOTR质粒转染到COS 7细胞中并进行了瞬时真核表达。结果 :将mOTR的羧基端和氨基端的cDNA片段亚克隆入了PMD 18 T载体。连接并最终获得了mOTR编码区的全长序列 ,构建了pEGFP N3 mOTR真核表达载体。将pEGFP N3 mOTR载体转染入COS 7细胞 ,并成功地进行了瞬时真核表达。结论 :成功构建了包含mOTR全长编码区序列的pEGFP N3 mOTR真核表达载体 ,并在COS 7细胞中进行了瞬时表达 ,为今后研究mOTR的功能打下了基础。     

beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG)

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.     

Parity mediates the association between infant feeding method and maternal depressive symptoms in the postpartum

Summary Maternal depression is the most common complication of the postpartum, having devastating and long lasting effects on mother and infant. Lactation is associated with attenuated stress responses, especially that of cortisol, and the lactogenic hormones, oxytocin and prolactin, are associated with anti-depressant and anxiolytic effects. These associations suggest that breast-feeding may decrease maternal depressive symptoms, yet empirical results have been conflicting. Recent findings have indicated that parity may mediate the association between breast-feeding and stress response. Because a decreased stress response is associated with a decreased risk for depression, parity may also mediate the association between infant feeding method and depressive symptoms. Specifically, the benefits of breast-feeding may appear in multiparous but not primiparous mothers. In the present study, data drawn from a national sample of primiparous and multiparous mothers were examined for possible associations between infant feeding method and depressive symptoms, as assessed by the Center for Epidemiological Survey-Depression scale (CES-D). After controlling for several possible confounding variables, breast-feeding by multiparas was associated with significantly decreased odds of having depression compared with bottle-feeders (OR = 0.41, CI 0.19–0.87, p = 0.02); however, no risk reduction from breast-feeding was evident among primiparas. The results support a parity-mediated association between lactation and maternal depressive symptoms. The results provide a reason for earlier conflicting findings, present new research avenues, and suggest possible clinical approaches. Correspondence: Elizabeth Sibolboro Mezzacappa, Ph.D., 93 Stony Road, Edison, NJ 08817-3726, U.S.A.     

盐皮质激素受体基因多态性与妊高征相关性研究

目的探讨中国人群中盐皮质激素受体基因(MR)外显子3上A760G多态性与妊高征的相关性.方法以人外周血DNA为模板,通过聚合酶链式反应-等位特异性寡核苷酸杂交(PCR-ASO)方法测定95例随机妇女、101例正常孕妇、60例妊高征妇女的MR外显子3上A760G多态性频率.结果MR外显子3上A760G多态性位点中A等位基因和C等位基因在正常孕妇组中分别为83.17%与16.83%,在妊高征组中分别为84.17%与15.83%,在随机人群组中分别为86.84%与13.16%.结论中国人群中MR基因外显子3上存在A760G多态性,该多态性与妊高征不存在相关性.     

G72基因与抑郁症的关联研究

目的探讨抑郁症与G72基因多态性的关系，以及是否有混合家族史的抑郁症其G72基因多态性有无区别。方法应用聚合酶链反应技术分别检测符合《中国精神障碍分类与诊断标准》的100例元混合家族史抑郁症、50例有混合家族史抑郁症、86名正常对照的G72基因的单核苷酸多态性rs947267、rs2181953，并进行关联分析。结果（1）女性无混合家族史抑郁症组与对照组rs947267基因型及等位基因分布频率，差异均有统计学意义（P=0．017、P=0．008），基因型A／A、等位基因A、C的OR值分别为0．300（P=0.010）、0．456（P=0．008）、2．195（P=0．008），而男性差异均无统计学意义（P〉0．05）；（2）不同性别无混合家族史抑郁症组与对照组rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0．05）；（3）不同性别有混合家族史抑郁症组与对照组rs947267、rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0.05）。结论G72基因多态性可能与女性无混合家族史的抑郁症患者存在关联，其中rs947267的C等位基因是危险因子。     

Association between dopamine D4 receptor (D4DR) Exon III polymorphism and novelty seeking in Japanese subjects

This study was designed to assess the association between novelty seeking and D4DR gene polymorphism in the Japanese population. The 48 bp repeat polymorphism in the third exon of the dopamine D4 receptor gene of 153 normal female students was correlated with personality feature results from the Japanese version of Cloninger's Temperament and Character Inventory. The Novelty Seeking subscale of Exploratory Excitability had a significant association with long alleles of the polymorphic exon III repeat sequence of D4DR. Our results suggest that there is an association between long alleles of the polymorphic exon III repeat sequence of D4DR and the personality traits of the Novelty Seeking subscale of Exploratory Excitability, regardless of racial differences in the frequencies of D4DR exon III repeat polymorphism. Am. J. Med. Genet. 74:501–503, 1997. © 1997 Wiley-Liss, Inc.     

晚期糖基化终产物受体基因多态性与空腹血糖水平的关联研究

目的 分析晚期糖基化终产物受体(receptor for advanced glycation endproducts,RAGE)的遗传变异与中国汉族人群高血糖的关系.方法 调查对象来自江苏省农村地区14469人群中,选取18～62岁成年对象共2731人进行空腹血糖水平流行病学调查;收集流行病学资料和体格检查资料并检测血糖等临床生化指标.位点选择采用连锁不平衡分析的方法,选取RAGE基因及其上游的3个tagSNPrs 1800624、rs204993、rs 184003进行基因分型和关联分析.结果 校正年龄、性别、体力活动和BMI混杂因素前后,rs1800624、rs204993和rs184003位点与血糖水平的关联均无统计学意义.不同基因型之间血糖水平比较也未发现上述3个SNP变异与血糖数量性状存在关联,进一步按性别因素进行分层分析,结果显示,在男性人群中,病例组rs184003位点的不同基因型与血糖水平关联有统计学意义,OR(95％ CI)为0.212～2.261,P值为0.01;校正年龄、体力活动指数和BMI混杂因素后,结果仍有统计学意义,OR(95％ CI)为0.064～2.305,P值为0.002.结论 未发现RAGE基因rs1800624、rs204993和rs 184003位点的变异与血糖水平存在显著关联.     

维吾尔族雌激素β受体基因多态性与妊娠期肝内胆汁淤积症的相关性分析

目的 探讨维吾尔族雌激素β受体(extrogen receptor beta gene,ERβ)基因多态性与妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)的相关性.方法 选择2008年4月至2011年4月在新疆医科大学第一附属医院分娩的维吾尔族ICP患者105例为观察组,105名同期维吾尔族正常孕妇作为对照组.应用限制性片段长度多态性方法分析rs1256049(RsaI)和rs4986938(Alu I)两个功能位点,观察两组孕妇ERβ基因型的分布.结果 Rsa I和Alu I的限制性片段长度多态性在两组中均呈多态性分布.ICP组R等位基因频率为35.71％,对照组为50.95％,OR值为0.535(95％可信区间为0.3619～0.7910,P＜0.01);ICP组A等位基因频率为21.43％,对照组为10.95％,OR值为2.2174(95％可信区间为1.2866～3.8215,P＜0.05).结论 维吾尔族孕妇ERβ基因多态性与ICP存在相关性,R等位基因可能是其保护因素,A等位基因则可能是风险因素.     

Novel polymorphisms in the upstream region of the human dopamine D4 receptor (DRD4) gene

We found nine novel polymorphisms in the upstream region of the human dopamine D4 receptor (DRD4) gene of Japanese by direct sequencing. These polymorphisms are −809G > A, −768G > A, −616C > G, −603T > del, −602G > del, −600G > C, −376C > T, −291C > T, and −128G > T. One known polymorphism, −521C > T, was also recognized. Six of these sites were identified as restriction fragment length polymorphisms (RFLPs). Received: June 11, 1999 / Accepted: June 23, 1999     

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, ?141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed. However, we found a slightly significant association between the ?141C Ins/Del polymorphism and the total Abnormal Involuntary Movement Scale (AIMS) score (P = 0.037). The significant association between the ?141C Ins/Del polymorphism and the total AIMS score did not remain after the regression analysis was taken into account (P = 0.14). Our results suggest that that three functional polymorphisms in DRD2 may not play a major role in the occurrence of TD. © 2001 Wiley‐Liss, Inc.     

Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorder

We selected 42 patients with bipolar disorder type I (BPI) and 40 healthy controls for genetic analysis of DNA polymorphisms in the serotonin receptor 2c (5-HTR2c) and serotonin transporter (5-HTT) genes. No significant associations were found in the total patient sample. However, when the individuals were divided according to gender, trends for association with both polymorphisms (P = 0.051 for 5-HTR2c and P = 0.049 for 5-HTT) in female patients were observed. These results suggest that variations in these genes may be responsible for a minor increase in susceptibility for bipolar disorder in women. Am. J. Med. Genet. 74:504–506, 1997. © 1997 Wiley-Liss, Inc.     

Analysis of the tyrosine hydroxylase and dopamine D4 receptor genes in a Croatian sample of bipolar I and unipolar patients

We selected 83 patients with bipolar disorder type I or unipolar recurrent major depression and 71 healthy controls for genetic analysis of the tyrosine hydroxylase and the dopamine D4 receptor gene. No significant association was found between bipolar disorder type I and unipolar recurrent major depression and the polymorphisms located near these genes. Therefore, the hypothesis that the tyrosine hydroxylase and the dopamine D4 receptor genes may be involved in the etiology of bipolar disorder and unipolar recurrent major depression is not supported in our study. Am. J. Med. Genet. 74:176–178, 1997. © 1997 Wiley-Liss, Inc.     

神经型烟碱乙酰胆碱受体α7亚单位基因多态性与精神分裂症的传递不平衡研究

目的 探讨神经型烟碱乙酰胆碱受体α7亚单位基因(neuronal nicotinic acetyleholine receptor α7 subunit gene,CHRNA7)多态性与精神分裂症的关系.方法 应用聚合酶链反应及聚丙烯酰胺凝胶芯片技术检测129个精神分裂症先证者核心家系CHRNA7基因的rs2337980、rs1909884、rs883473三个单核苷酸多态性,并采用基于单倍型的单倍型相对风险检验(haplotype relative risk,HHRR)、传递不平衡检验(transmission disequilibrium test,TDT)及单倍型分析进行统计.结果 (1)HHRR分析结果显示rs2337980位点精神分裂症患者组与虚拟对照组之间等位基因频率差异有统计学意义(P=0.017);(2)TDT分析发现,rs2337980位点与精神分裂症之间可能存在传递不平衡,杂合子父母过多的传递等位基因C给患病子女(P=0.021).(3)单倍型分析发现,rs2337980、rsl909884及rs2337980、rsl909884、rs883473组成的单倍型与精神分裂症有显著相关(总体P=0.034;glohal P=0.027),其中T-C,T-C-T两个单倍型与精神分裂症可能存在传递不平衡.结论 CHRNA7 基因多态性可能与精神分裂症存在关联,rs2337980的变异等位基因T可能是精神分裂症的保护性因子.     

Genetic contribution of tumor necrosis factor (TNF)-alpha gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility

PROBLEM: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis. METHODS OF STUDY: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) - preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively. RESULTS: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls. CONCLUSION: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms.