Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of an X chromosome-linked immune deficiency gene (xid) on several properties of the anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 (NAF1) mice was examined. With respect to response magnitude, it was found that male, xid-expressing NAF1 mice showed about 1/3 the concentration of serum anti-Ar antibody as normal female NAF1 mice in hyperimmune responses to Brucella abortus (BA)-Ar. In responses induced by keyhole limpet hemocyanin (KLH)-Ar, males showed responses of about 1/8 to 1/2 the female levels, depending on the assay time point. The kinetics of the latter response were identical in mice of the two sexes. No significant difference could be detected in the time-dependent avidity maturation of the anti-Ar antibody elicited by KLH-Ar in xid vs. normal mice. The isotype profile of the day 38 anti-Ar primary response elicited by KLH-Ar in male NAF1 mice differed from that of the female mice in two ways: IgG2a levels were depressed, and a significantly lower number of the male mice demonstrated detectable IgG3 anti-Ar antibody production. The primary focus of htis work was to determine the effect of xid on the expression of the major cross-reactive idiotype--CRIA--of A strain mice. It was found that while a significant higher proportion of the female mice could be classified as high CRIA producers in responses to BA-Ar, no difference could be demonstrated if the inducing antigen was KLH-Ar. It is proposed that the difference observed with the two antigens may be due to the more selective activation by KLH-Ar of a small subset of high affinity Ar-specific clones--which may be enriched for CRIA + precursors--in both normal and immune defective mice. In contrast, BA-Ar may 'sample' more of the total anti-Ar repertoire and thus reveal within it an xid-determined depression in the proportion of CRIA + clones. Finally, it is noted that the influence of xid appears to be largely of a stochastic, and not an absolute character.
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PMID:Influence of xid on anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 mice: differential idiotype expression induced by only one of two Ar antigens. 310 63

A limited number of genetic variants have been identified in traditional GWAS as risk or protective factors for alcohol use disorders (AUD) and related phenotypes. We herein report whole-genome association and rare-variant analyses on AUD traits in American Indians (AI) and European Americans (EA). We evaluated 742 AIs and 1711 EAs using low-coverage whole-genome sequencing. Phenotypes included: (1) a metric based on the occurrence of 36 alcohol-related life events that reflect AUD severity; (2) two alcohol-induced affective symptoms that accompany severe AUDs. We identified two new loci for alcohol-related life events with converging evidence from both cohorts: rare variants of K2P channel gene KCNK2, and rare missense and splice-site variants in pro-inflammatory mediator gene PDE4C. A NAF1-FSTL5 intergenic variant and an FSTL5 variant were respectively associated with alcohol-related life events in AI and EA. PRKG2 of serine/threonine protein kinase family, and rare variants in interleukin subunit gene EBI3 (IL-27B) were uniquely associated with alcohol-induced affective symptoms in AI. LncRNA LINC02347 on 12q24.32 was uniquely associated with alcohol-induced depression in EA. The top GWAS findings were primarily rare/low-frequency variants in AI, and common variants in EA. Adrenal gland was the most enriched in tissue-specific gene expression analysis for alcohol-related life events, and nucleus accumbens was the most enriched for alcohol-induced affective states in AI. Prefrontal cortex was the most enriched in EA for both traits. These studies suggest that whole-genome sequencing can identify novel, especially uncommon, variants associated with severe AUD phenotypes although the findings may be population specific.
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PMID:Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the "dark side" of addiction. 3071 57