The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3.

Objectives: Methamphetamine (METH) is a central nervous psychostimulant and one of the most frequently used illicit drugs. Numerous genetic loci that influence complex traits, including alcohol abuse, have been discovered; however, genetic analyses for METH dependence remain limited. An increased histone deacetylase 3 (HDAC3) expression has been detected in Fos-positive neurons in the dorsomedial striatum following withdrawal after METH self-administration. Herein, we aimed to systematically investigate the contribution of HDAC3 to the vulnerability to METH dependence in a Han Chinese population. Methods: In total, we recruited 1,221 patients with METH dependence and 2,328 age- and gender-matched controls. For genotyping, we selected 14 single nucleotide polymorphisms (SNPs) located within ± 3 kb regions of HDAC3. The associations between genotyped genetic polymorphisms and the vulnerability to METH dependence were examined by single marker- and haplotype-based methods using PLINK. The effects of expression quantitative trait loci (eQTLs) on targeted gene expressions were investigated using the Genotype-Tissue Expression (GTEx) database. Results: The SNP rs14251 was identified as a significant association signal (χ2 = 9.84, P = 0.0017). An increased risk of METH dependence was associated with the A allele (minor allele) of rs14251 [odds ratio (95% CI) = 1.25 (1.09-1.43)]. The results of in silico analyses suggested that SNP rs14251 could be a potential eQTL signal for FCHSD1, PCDHGB6, and RELL2, but not for HDAC3, in various human tissues. Conclusion: We demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.

Application Prospect of Integrative Omics in Forensic Identification of Methamphetamine-Associated Psychosis.

The clinical symptoms and signs of methamphetamine-associated psychosis (MAP) and schizophrenia are highly similar, but the situation is completely different when MAP and schizophrenia patients need to be assessed for criminal responsibility after they comitted a harmful behavior. Therefore, the distinction between the two psychoses is very important in forensic psychiatry. At present, the identification of these two psychoses is mainly dependent on the corresponding criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It's challenging to diagnose and distinguish between the two in practical cases due to their similar clinical symptoms and the lack of effective objective indexes. Different from the limitations of single omics, integrative omics intergrates data from multiple dimensions and has been extensively studied in the field of schizophrenia and has achieved some preliminary results. In view of the correlation between MAP and schizophrenia and the potential application value of integrative omics, this paper proposes an integrative omics strategy for MAP pathogenesis and forensic identification, aiming to improve the further understanding of the relationship between the two psychoses and the corresponding pathogenesis. It also provides references for the future exploration of integrative omics in forensic precise identification and effective monitoring and early warning methods.

Common Variants in NUS1 and GP2 Genes Contributed to the Risk of Gestational Diabetes Mellitus.

Background: Recently, NUS1 and GP2 genes were reported to be associated with the risk of type 2 diabetes (T2D) in a Japanese population. Given the sharing of pathogenic contribution from genetic factors between T2D and gestational diabetes mellitus (GDM), we conducted the study to systematically examine the relationship of NUS1 and GP2 genes with the susceptibility to GDM in Chinese Han population. Methods: A total of 4,250 subjects comprised of 1,282 patients with GDM and 2,968 controls were recruited, and 20 tag single nucleotide polymorphisms (SNPs) (10 from NUS1 and 10 from GP2) were selected for genotyping. Association analyses were conducted for GDM and its related biomedical indexes including fasting glucose and HbA1c levels. Results: Two SNPs, rs80196932 from NUS1 (P=2.93×10-5) and rs117267808 from GP2 (P=5.68×10-5), were identified to be significantly associated with the risk of GDM. Additionally, SNP rs80196932 was significantly associated with HbA1c level in both patients with GDM (P=0.0009) and controls (P=0.0003), while SNP rs117267808 was significantly associated with fasting glucose level in both patients with GDM (P=0.0008) and controls (P=0.0007). Serum levels of protein NUS1 and GP2 were measured for the study subjects, and significant differences were identified among groups with different genotypes of SNP rs80196932 and rs117267808, respectively. Conclusions: Our findings indicate that NUS1 and GP2 genes contribute to the risk of GDM, which would help to offer the potential to improve our understanding of the etiology of GDM and, in turn, could facilitate the development of novel medicines and treatments for GDM.

Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population.

A recent genome-wide meta study suggested that rs67338227 in the FHL5 gene and rs10456100 in the KCNK5 gene are associated with migraine from 27 population-based cohorts excluding Chinese population. Given that migraine without aura (MO) is the most common subtype of migraine, our aim was to systematically investigate the relationship of common variants in FHL5 and KCNK5 genes with the susceptibility to MO and provide clues as to the nature of the mechanisms involved in the etiology of migraine. A total of 3306 subjects including 1042 patients with MO and 2264 controls were recruited for the discovery stage, and 2530 individuals including 842 patients with MO and 1688 controls for the replication stage. Twenty-two tag SNPs (7 from FHL5 and 15 from KCNK5) were selected for genotyping. Genetic associations were analyzed at both single-marker and haplotype levels. Potential functional consequences of the significant SNPs were analyzed using gene expression data obtained from the GTEx database. Two SNPs, rs10456100 (KCNK5, P = 9.01 × 10-9) and rs7775721 (FHL5, P = 6.86 × 10-13), were determined to be significantly associated with MO in the discovery sample and were then replicated in another sample. In the combined sample set, the T allele of both SNPs was significantly associated with the increased risk of MO. Significant eQTL signals were identified for both SNP rs10456100 and rs7775721. Our findings suggest that the T allele carriers of SNP rs10456100 and rs7775721 are at increased risk of migraine.

Genetic Polymorphisms of RGS14 and Renal Stone Disease.

BACKGROUND: Renal stone disease (RSD) is a common disease of the human urinary system and is regarded as a multifactorial condition affected by environmental and genetic factors. RGS14 encodes a complex scaffolding protein, known as regulator of G protein signaling 14, which is enriched in hippocampal area CA2 dendritic spines. AIM OF THE STUDY: We aimed to investigate the association between genetic polymorphisms in RGS14 and the risk of RSD based on a large sample of the Chinese Han population. METHODS: A total of 1,436 subjects, comprising 506 patients with RSD and 920 controls, were enrolled in the study. Ten tag SNPs located in the RGS14 gene region were chosen for genotyping. Genetic associations were evaluated at both the single marker and haplotype levels. Genotypic (χ2 test) and allelic analyses (Cochran-Armitage test for trend) were performed for single marker-based association. Two bioinformatics tools, RegulomeDB and GTEx, were used to examine the functional consequences of the target SNP. RESULTS: SNP rs11746443 was found to be significantly associated with disease status (χ2 = 12.60, p = 0.0018). Moreover, the A allele of this SNP was significantly associated with an increased risk of RSD (OR [95%CI] = 1.36 [1.13-1.65]). Multiple significant eQTL signals of rs11746443 on RGS14 were identified. CONCLUSIONS: This study replicated the association signal of RGS14 with RSD in a large sample of the Chinese Han population. The results suggest that the SNP rs11746443 of RGS14 might increase the risk of RSD by regulating the Ca2+ levels in humans.

Application of CD83 and HSF5 to Identify Antemortem and Postmortem Skin Burns. / 应用CD83和HSF5鉴别生前与死后皮肤烧伤.

OBJECTIVES: To explore the forensic application value of cluster of differentiation 83 (CD83) and heat shock transcription factor 5(HSF5) in identifying antemortem and postmortem skin burns. METHODS: Through reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR), CD83 and HSF5 mRNA levels in the skin tissues of antemortem and postmortem burned mice and human samples were detected quantitatively. RESULTS: Compared with the control group and the postmortem burned group, the mRNA levels of CD83 and HSF5 in antemortem burned mice were higher. The high mRNA expressions of CD83 could be detected 96 h after death, and the mRNA expressions of HSF5 could be observed 72 h after death. Compared with undamaged skin, increased CD83 and HSF5 mRNA levels were detected in 11 out of 15 cases(P<0.05). CONCLUSIONS: CD83 and HSF5 can be used in forensic practice as indicators for vital reaction in antemortem burn identification.