Association of Tryptophan Hydroxylase-2 Gene rs4290270 with Primary Insomnia and Depressive Symptoms in a Chinese Han Population

Abstract

Background:Insomnia often coexists with depression, and there is compelling evidence for a genetic component in the etiologies of both disorders.Aims:To investigate the relationship between exonic variant (rs4290270) in the tryptophan hydroxylase-2 gene and primary insomnia and symptoms of depression in Han Chinese.Study Design:Case-control study.Methods:This study included 152 patients with primary insomnia and 164 age- and gender-matched normal controls. All patients were investigated by polysomnography for 2 consecutive nights. The depressive symptoms were measured by using a 20-item Zung Self-rating Depression Scale. Sleep quality was assessed with the Pittsburgh Sleep Quality index. The genotypes of the TPH-2 gene polymorphism rs4290270 were determined by the polymerase chain reaction-restriction fragment length polymorphism method.Results:The genotype distributions of the tryptophan hydroxylase-2 gene polymorphism rs4290270 were in Hardy-Weinberg equilibrium in both patients and controls (p>0.05). The allele and genotype distributions of this variant were comparable between patients and controls in all subjects and between genders (all p>0.05). The impact of rs4290270 on self-rating depression scale score changes was statistically significant (p=0.002), with carriers of the A/A genotype having the highest self-rating depression scale score (mean ± standard deviation: 52.73±12.88), followed by the A/T genotype (50.94±11.29, p=0.35) and the T/T genotype (43.48±7.78, p<0.01), and this impact was more obvious in women (p<0.001).Conclusion:The tryptophan hydroxylase-2 gene polymorphism rs4290270 may not be a susceptibility locus for primary insomnia in Han Chinese, but it may be a marker of depressive symptoms.

TPH-2 Gene Polymorphism in Major Depressive Disorder Patients With Early-Wakening Symptom

“…rs4290270 was prominently associated to the early wakening MDD group rather than the whole MDD group and non-early wakening MDD group. This result was consistent with a previous study which reported that rs4290270 served as a biomarker for depression patients with primary insomnia in Han Chinese population ( Mei et al, 2018 ). In the past, rs4290270 showed an association between symptoms of disturbed sleep and MDD ( Utge, 2012 ).…”

“…TPH-2 has been widely debated as a major candidate gene in numerous psychiatric disorders including MDD, anxiety, schizophrenia, and bipolar disorder ( Zill et al, 2004 ). Numerous candidate TPH-2 variants, namely rs4290270 ( Shen et al, 2011 ; Wang et al, 2015 ; Karanovic et al, 2017 ; Mei et al, 2018 ), rs4570625 ( Gao et al, 2012 ; Mandelli et al, 2012 ; Lehto et al, 2015 ; Han et al, 2017 ; Piel et al, 2018 ; Wigner et al, 2018 ), rs41317118 ( Xu et al, 2013 ), rs11178998 ( Xu et al, 2016 ; Ottenhof et al, 2018 ), rs7305115 ( Ke et al, 2006 ; Van der Auwera et al, 2014 ; Wang et al, 2015 ; Ottenhof et al, 2018 ), rs17110747 ( Tsai et al, 2009 ; Ottenhof et al, 2018 ), rs10748185 ( Serretti et al, 2011 ; Ottenhof et al, 2018 ), rs18438099 ( Anttila et al, 2009 ; Ottenhof et al, 2018 ), rs11316791, rs1386493, rs1386494 ( Haghighi et al, 2008 ), have been prominently associated with MDD. The exonal variants, rs7305115 and rs4290270, were prominently associated with MDD and disturbed sleep ( Utge, 2012 ; Mei et al, 2018 ).…”

Association between 5‐hydroxytryptamine gene polymorphism rs140700 and primary insomnia in Chinese population

“…For instance, the 5-HT system was found to participate in the regulation of sleep and wake statues. 26 1,[28][29][30] However, these risk factors cannot fully predict the risk for insomnia. An increasing number of genes and variants have been examined as promising candidate risk factors for insomnia.…”

“…Data were excluded in cases of a normal sleeping state affected by accommodation condition. The following polysomnography indexes were assessed: (i) sleep efficiency; (ii) total sleep time; (iii) sleep latency; (iv) arousal index; (v) percentage of stage 1 (S1%), stage 2 (S2%), stage 3 (S3%) and stage 4 (S4%): the proportion of stage 1, stage 2, stage 3 and stage 4, respectively, to the total sleep time 1,22 …”

“…Insomnia is a serious worldwide issue. 1 Long-term insomnia has been found to cause anxiety, depression, memory loss, 2 low immunity and increased risks of cardiovascular diseases, such as cerebrovascular disease, hypertension, diabetes, as well as dementia, mental illness and skeletal muscle disease. 3 It is also a cause of increased mortality from heart disease.…”