A family-based association study of the HTR1B gene in eating disorders

Objective: To explore the association of three polymorphisms of the serotonin receptor 1Dβ gene (HTR1B) in the etiology of eating disorders and their relationship with clinical characteristics. Methods: We analyzed the G861C, A-161T, and A1180G polymorphisms of the HTR1B gene through a family-based association test (FBAT) in 245 nuclear families. The sample was stratified into anorexia nervosa (AN) spectrum and bulimia nervosa (BN) spectrum. In addition, we performed a quantitative FBAT analysis of anxiety severity, depression severity, and Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) in the AN and BN-spectrum groups. Results: FBAT analysis of the A-161T polymorphism found preferential transmission of allele A-161 in the overall sample. This association was stronger when the sample was stratified by spectrums, showing transmission disequilibrium between the A-161 allele and BN spectrum (z = 2.871, p = 0.004). Quantitative trait analysis showed an association between severity of anxiety symptoms and the C861 allele in AN-spectrum participants (z = 2.871, p = 0.004). We found no associations on analysis of depression severity or preoccupation and ritual scores in AN or BN-spectrum participants. Conclusions: Our preliminary findings suggest a role of the HTR1B gene in susceptibility to development of BN subtypes. Furthermore, this gene might have an impact on the severity of anxiety in AN-spectrum patients.

Association study of HTR1A and HTR1B with adolescent idiopathic scoliosis / 中华外科杂志

<p><b>OBJECTIVE</b>To assess whether HTR1A and HTR1B polymorphisms are associated with the predisposition, gender, PUMC Classification and/or severity of adolescent idiopathic scoliosis (AIS).</p><p><b>METHODS</b>Rs6294 (HTR1A) and rs6296 (HTR1B) were genotyped in 103 AIS patients treated from January 2006 to March 2007, and 108 controls with matched gender and age. The data were analyzed by the allelic and genotypic association analysis, and the genotype-phenotype (gender, PUMC Classification, and Cobb angle) association analysis.</p><p><b>RESULTS</b>The distributions of the alleles of all the 2 SNPs met Hardy-Weinberg equilibrium in the controls (goodness-of-fit chi(2) test, P > 0.05). The allele A of rs6294 was related with the occurrence of AIS (P = 0.041), but differences of the allele frequencies of rs6296 and the genotype frequencies of both SNPs between 2 groups had no statistical significance (P > 0.05). The genotype A/A + A/G of rs6294 was associated with AIS PUMC type III, and there was no other positive results in genotype-phenotype association analysis.</p><p><b>CONCLUSION</b>These results suggest that HTR1A may be a predisposition gene of AIS PUMC type III, and PUMC Classification may has its genetic basis.</p>

Regional Distribution of 5-HT 1A, 1B, and 1D Receptors in Rat Vestibular Nuclei (Vn) and Inner Ear

Migraine and anxiety disorders are frequently co-morbid with balance disorders. Potential mechanisms for migrainous vertigo include sites of action of 5-HT (serotonin) 1B and 1D receptor agonists such as rizatriptan, which attenuate motion sickness in migraineurs. Selective serotonin reuptake inhibitors (SSRIs) are also known to be efficacious in the treatment of vertigo. Relative distribution of the 5-HT receptor subtypes and their functional roles in the vestibular nuclei and inner ear is still unknown. Using 5-HT1A, 1B, AND 1D receptors-specific antibody, we have demonstrated a differential distribution of these receptor subtypes within the rat vestibular nuclei and inner ear. For 5-HT receptor subtypes expression in the vestibular and auditory periphery, most ganglion cells in the vestibular ganglion showed immunoreactivity for 5-HT1A, 5-HT1B and 5-HT1D receptors. In addition, 5-HT1B and 1D receptors immunopositive reactivities were associated with endothelial cells of small blood vessels in the vestibular ganglion and nerve, endothelial cells in both the spiral ligament deep to the spiral prominence and stria vascularis and endothelial cells on blood vessels along the margins of the spiral ganglion. For 5-HT receptor subtypes expression in the vestibular nuclei (VN), the 5-HT1A, 1B and 1D receptors were expressed differentially in the VN. Fine varicose axons in the periventricular plexus showed intense 5-HT1A receptor expression in the medial VN (MVN) and extended into the superior VN (SVN). By contrast, 5-HT1B receptors were not expressed the ventricular plexus axons. Rather, 5-HT1B and 1D receptors immunopositive cell bodies and neuronal processes were dense in rostral MVN, dorsal SVN, lateral VN (LVN) and ventral aspect of nucleus prepositus hypoglossi (NPH). In the present study, inner ear and vestibular nuclei showed distinct distributions of 5- HT1A, 1B and 1D receptors expressions that are parallel to their distribution in peripheral and central nociceptive pathways. These differentially distributed 5-HT receptor subtypes are potential targets to explain the efficacy of SSRIs and triptans in treating migraine and migrainous vertigo.

Polymorphisms in 5-HT1Dbeta Receptor Gene and Personality Traits in a Korean Population / 신경정신의학

OBJECTIVES: Recently, there has been a growing enthusiasm in biological approach to personality; the identification of genes responsible for particular personality traits. The aim of this study was to investigate the association between the 5-HT1Dbeta G861C polymorphism and personality traits. METHODS: We recruited 218 normal subjects. The Korean version of the Temperament and Character Inventory (TCI) was used to assess personality traits. From blood samples taken from the subjects, DNA was isolated using standard techniques and the HT1Dbeta G861C polymorphism was genotyped by means of polymerase chain reaction and Homogeneous MassEXTEND method. We classified the subject into the GG, CG, and GG groups according to their genotypes. The differences in the temperament factors of the TCI between homozygote group (GG+CC genotype) and heterozygote group (CG genotype) were tested. RESULTS: The heterozygote group had significantly lower Harm avoidance (HA) scores and higher Self-directedness scores (SD) than the homozygote group. CONCLUSION: In conclusion, we found some associations between the 5-HT1Dbeta G861C polymorphism and the personality dimension HA and SD in a normal population.

Association between Serotonin 2A(T102C) and 1B(G861C) Receptor Gene Polymorphism and Suicidal Attempt with Drug Intoxication in Korean Populations

OBJECTIVES: Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. METHODS: The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan(R) assay using primers based on previous studies. RESULTS: The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). CONCLUSION: These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

A Family-Based and Case-Control Association Study of the Serotonin 1B Receptor Gene Polymorphism in Korean Attention Deficit Hyperactivity Disorder

OBJECTIVE: Attention deficit hyperactivity disorder(ADHD) is the most common childhood psychiatric disorder, affecting 3-5% of school-aged children. Although the biological basis of ADHD is unknown, family studies provide strong evidence that ADHD has a genetic basis. Recent genetic studies have suggested associations between ADHD and serotonin 1B(5HT1B) receptor gene G861C polymorphism. The aim of this study is to test for the association between ADHD and 5HT1B receptor gene G861C polymorphism in Korean population. METHOD: We processed DNA extraction and genotyping. 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT) and haplotype-based haplotype relative risk (HHRR). And the ADHD children were compared with 212 age and gender matched normal controls. RESULTS: There was no statistical difference of distributions between ADHD cases and controls. We did not observe any preferential transmission of alleles of 5HT1B receptor gene G861C polymorphism in ADHD. CONCLUSIONS: Though there is the possibility of failing to detect small genetic effects, our results show no evidence of an association between ADHD and 5HT1B receptor gene G861C polymorphism in the Korean population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to ADHD.