GENETICS OF GENERALIZED ANXIETY DISORDER

Autor: Pomohaibo, V., Berezan, O., Petrushov, A.
Jazyk: ukrajinština
Rok vydání: 2020
Předmět:
Zdroj: Psychology and Personality; № 2 (2020); 280-291
Психологія і особистість; № 2 (2020); 280-291
ISSN: 2226-4078
2410-3527
Popis: The essential feature of generalized anxiety disorder (GAD) is excessive anxiety and worry about various spheres of own life. Its prevalence ranges from 0,4% to 3,6%. The genetic share of GAD is about 32%. The rest is an influence of environmental factors, of which the most significant are childhood adversities and parental overprotection. In consequence of such features the genetic study of GAD is very difficult.To reveal candidate genes for GAD the genetic study of brain neurotransmitters is dominated. Now there are proposed over 20 genes, which has been associated with GAD.First candidate gene was proposed by D.C. Rowe with colleagues in 1998. It was the dopamine transporter gene (DAT1; modern gene symbol is SLC6A3; 5p15.33). The disorder symptoms are increased with a greater number of 10 tandem repeats of a 40 bp fragment in the 3’UT region of DAT1 gene. In following year K. Ohara with colleagues obtained a significant similar result for the serotonin transporter gene (5-HTT; modern gene symbol is SLC6A4; 17q11.2). In this study tandem repeats of 17 bp have been identified in the second intron of the gene. The 5-HTT gene variants are associated also with over 80 different diseases. Later A. Tadic with colleagues found a significant association between GAD and single nucleotide polymorphism (SNP) T941G (rs6323) in exon 8 of the monoamine oxidase A gene (MAOA; Xp11.3). In the MAOA gene uVNTR promoter J. Samochowiec with colleagues discovered an association between GAD and an increase of tandem repeats of 30 bp number over 3. In the study of J.S. You with colleagues there was showed the significant involvement of short alleles of the 5-HTT gene (allase SLC6A4) in GAD, but there is not confirmed the involvement of variable number tandem repeats in this gene, as shown by Japanese authors. Short allele of 5-HTT contains 14 tandem repeats of a 22 bp vs normal 16 in the 5-HTTLPR intron region near the promoter.In addition, the J.M. Hettema’s group of American psychiatrists proposed three GAD candidate genes – the GAD1 (Glutamate Decarboxylase 1; 2q31.1), the HTR1A (Serotonin Receptor 1A; 5q12.3) and the COMT (Catechol-O-methyltransferase; 22q11.21). Several SNPs were related to GAD: three SNPs (rs2241165, rs2058725 and rs3791850) were localized in the GAD1 gene introns, one (rs6295) – in the HTR1A gene promoter and two in the COMT gene (rs4680 – in exon and rs165599 – in the 3’UTR).A study dedicated to assessing the effects of exposure to the 2004 Florida hurricane reported increased risk of GAD in relation to SNP in the 3’UTR (rs4606) of the RGS2 gene (Regulator of G-Protein Signaling 2; 1q31.2) and SNP in the promoter region (rs16147) of the NPY gene (Neuropeptide Y; 7p15.3).A. J. Cooper with colleagues suggested some more two candidate genes for GAD: the hypophysis activating hormone (PACAP; allase ADCYAP1; 18p11.32) and the opioid receptor 1(OPRM1; allase MOR1; 6q25.2). In the PACAP gene SNP Asp54Gly (rs2856966) was involved in GAD. It was located in exon 2 of the gene. There was also showed a small correlation between SNP A118G (rs1799971; Asn40Asp) in exon 1 of the OPRM1 gene and GAD.All these results should be taken quite critically. First, the study was carried out on a statistically small samples of a few hundred people. Second, the results of these studies was not confirmed by other authors for samples of a few thousand people. GAD problems remains relevant and requires further intense research efforts.
безпідставною стійкою надмірною тривожністю та переживаннями стосовно різних сфер власного життя. На цей час різні дослідники пропонують понад 20 генів, які можуть бути пов’язані з РЗТ. Найбільш вірогідними кандидатними генами РЗТ є ген транспортера дофаміну DAT1 (сучасний символ SLC6A3; 5p15.33), ген транспортера серотоніну 5-HTT (сучасний символ SLC6A4; 17q11.2), ген моноаміноксидази А MAOA (Xp11.3), ген декарбоксилази глютамінової кислоти 1 GAD1 (2q31.1), ген рецептора серотоніну 1А HTR1A(5q12.3), ген катехол-О-метилтрансферази COMT (22q11.21), ген регулятора сигналізації 2 G-протеїнів RGS2 (1q31.2), ген регулятора збудливості кори головного мозку NPY (7p15.3), ген гормону активності гіпофізу (PACAP; синонім ADCYAP1; 18p11.32) та ген опіоїдного рецептора 1 (OPRM1; синонім MOR1; 6q25.2). Усі ці результати необхідно сприймати досить критично. По-перше, дослідження були здійснені на статистично недостатніх вибірках всього в кілька сотень осіб. По-друге, результати цих досліджень поки-що достовірно не підтверджені іншими авторами на вибірках у кілька тисяч осіб. Проблема РЗТ залишається вельми актуальною і потребує подальших інтенсивних зусиль дослідників.
Databáze: OpenAIRE
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