Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia.
Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia.
复制标题
DOI：
10.1007/s00439-011-0989-6
复制
发表时间：
2011-11
期刊：
影响因子：
5.3
通讯作者：
Elston RC
中科院分区：
文献类型：
--
作者：
Cubells JF;Sun X;Li W;Bonsall RW;McGrath JA;Avramopoulos D;Lasseter VK;Wolyniec PS;Tang YL;Mercer K;Pulver AE;Elston RC
多巴胺β-羟化酶（DβH）催化多巴胺转化为去甲肾上腺素。DβH从交感神经元和肾上腺髓质囊泡释放后进入血浆。血浆DβH活性（pDβH）在个体之间差异很大，遗传遗传调节这种差异。连锁研究表明pDβH与9 q34上的ABO有很强的连锁关系，并有阳性证据表明与19p13.2-13.3上的补体结合位点有连锁关系。随后的关联研究强烈支持DBH，它与ABO相邻，是调节pDβH大部分遗传变异的基因座。先前的研究表明，pDβH的变异或DβH的遗传变异与精神分裂症和其他特发性或药物诱导的脑部疾病患者的精神病性症状表达差异相关，表明DBH可能是精神病性症状的遗传修饰剂。作为研究这一假设的第一步，我们对精神分裂症患者及其亲属的pDβH进行了连锁分析。结果强烈证实了在几种模型下（最大多点LOD得分，6.33），标记在DBH到pDβH的连锁，但没有发现证据支持连锁在染色体19上的任何地方。考虑到在DBH处的三个SNPs对连锁信号的贡献，rs 1611115、rs 1611122和rs6271降低但没有消除连锁峰，而考虑到在DBH附近的所有SNPs完全消除了信号。全基因组标记分析发现了染色体20 p12标记之间连锁的阳性证据（多点LOD = 3.1，27.2 cM）。本研究首次提供了DBH与pDβH连锁的直接证据，表明rs 1611115、rs 1611122、rs6271和DBH附近的其他未知变异体参与了pDβH的遗传调控，并表明20 p12附近的一个位点也影响pDβH。
Dopamine β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine. DβH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DβH activity (pDβH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDβH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDβH. Prior studies have suggested that variation in pDβH, or genetic variants at DβH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDβH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDβH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pDβH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDβH, and suggest that a locus near 20p12 also influences pDβH.
登录
查看更多内容
影响因子：
6.7
作者：
HEALY, MJR
通讯作者：
HEALY, MJR
影响因子：
1.8
作者：
Shete, S;Jacobs, KB;Elston, RC
通讯作者：
Elston, RC
影响因子：
11.4
作者：
LAMOUROUX, A;VIGNY, A;MALLET, J
通讯作者：
MALLET, J
DOI：
10.1159/000132584
发表时间：
1988-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
CRAIG, SP;BUCKLE, VJ;CRAIG, IW
通讯作者：
CRAIG, IW
影响因子：
4.9
作者：
Chen Y;Wen G;Rao F;Zhang K;Wang L;Rodriguez-Flores JL;Sanchez AP;Mahata M;Taupenot L;Sun P;Mahata SK;Tayo B;Schork NJ;Ziegler MG;Hamilton BA;O'Connor DT
通讯作者：
O'Connor DT