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- Tikkanen, R., et al.
(författare)
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Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men
- 2016
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 124:9, s. 529-534
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Tidskriftsartikel (refereegranskat)abstract
- Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5h oral glucose tolerance test using a 75g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.
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- Tiihonen, J, et al.
(författare)
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Genetic background of extreme violent behavior
- 2015
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 20:6, s. 786-792
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Tidskriftsartikel (refereegranskat)
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- Rautiainen, MR, et al.
(författare)
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Genome-wide association study of antisocial personality disorder
- 2016
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:9, s. e883-
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.
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- Tikkanen, R, et al.
(författare)
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Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon
- 2015
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5, s. e681-
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Tidskriftsartikel (refereegranskat)abstract
- A relatively common stop codon (Q20*) was identified in the serotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown–Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption. Regression analyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior.
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