BACKGROUND: Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches.
METHODS: In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach.
RESULTS: Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena.
CONCLUSIONS: Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.

OBJECTIVE: This study aims to systematically review the existing literature and critically appraise the evidence of genome-wide association studies (GWAS) on periodontitis. This study also aims to synthesise the findings of genetic risk variants of periodontitis from included GWAS.
METHODS: A systematic search was conducted on PubMed, GWAS Catalog, MEDLINE, GLOBAL HEALTH and EMBASE via Ovid for GWAS on periodontitis. Only studies exploring single-nucleotide polymorphisms(SNPs) associated with periodontitis were eligible for inclusion. The quality of the GWAS was assessed using the Q-genie tool. Information such as study population, ethnicity, genomic data source, phenotypic characteristics(definition of periodontitis), and GWAS methods(quality control, analysis stages) were extracted. SNPs that reached conventional or suggestive GWAS significance level(5e-8 or 5e-06) were extracted and synthesized.
RESULTS: A total of 15 good-quality GWAS on periodontitis were included (Q-genie scores ranged from 38-50). There were huge heterogeneities among studies. There were 11 identified risk SNPs (rs242016, rs242014, rs10491972, rs242002, rs2978951, rs2738058, rs4284742, rs729876, rs149133391, rs1537415, rs12461706) at conventional GWAS significant level (p<5x10-8), and 41 at suggestive level (p<5x10-6), but no common SNPs were found between studies. Three SNPs (rs4284742 [G], rs11084095 [A], rs12461706 [T]) from three large studies were from the same gene region-SIGLEC5.
CONCLUSIONS: GWAS of periodontitis showed high heterogeneity of methodology used and provided limited SNPs statistics, making identifying reliable risk SNPs challenging. A clear guidance in dental research with requirement of expectation to make GWAS statistics available to other investigators are needed.

Chronic inflammation is recognized as a major risk factor for cancer and is involved in every phase of the disease. Inflammasomes are central to the inflammatory response and play a crucial role in cancer development. The present review summarizes the role of Nod‑like receptor C4 (NLRC4) in inflammation and colorectal cancer (CRC). Reviews of the literature were conducted using Web of Science, PubMed and CNKI, with search terms including \'NLRC4\', \'colorectal cancer\', \'auto‑inflammatory diseases\' and \'prognosis\'. Variants of NLRC4 can cause recessive immune dysregulation and autoinflammation or lead to ulcerative colitis as a heterozygous risk factor. Additionally, genetic mutations in inflammasome components may increase susceptibility to cancer. NLRC4 is considered a tumor suppressor in CRC. The role of NLRC4 in CRC signaling pathways is currently understood to involve five key aspects (caspase 1, NLRP3/IL‑8, IL‑1β/IL‑1, NAIP and p53). The mechanisms by which NLRC4 is involved in CRC are considered to be threefold (through pyroptosis, apoptosis, necroptosis and PANoptosis; regulating the immune response; and protecting intestinal epithelial cells to prevent CRC). However, the impact of NLRC4 mutations on CRC remains unclear. In conclusion, NLRC4 is a significant inflammasome that protects against CRC through various signaling pathways and mechanisms. The association between NLRC4 mutations and CRC warrants further investigation.

Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility.

Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene; however, their results remain inconclusive. Thus, a systematic review and meta-analysis were carried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic search of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until 25 June 2024, and a reference list of relevant articles was collected, which explored the association between the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model, and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 182 studies, with 1888 cases (DR) and 2285 controls (without DR), were included in the meta-analysis. A statistically significant association between the rs1501299 polymorphism and the DR risk was recorded in G vs. T in the overall analysis (OR = 0.84, 95% CI = 0.72-0.99, p = <0.05, I2 = 23%, n = 5 studies). Additionally, the summary results in the subgroup analysis according to the control type were as follows: the DR versus diabetes mellitus (DM) control type revealed a statistically significant association in G vs. T: OR = 0.81, 95% CI = 0.67-0.97, p = <0.05, I2 = 27%, n = 4 studies; GG vs. GT: OR = 0.72, 95% CI = 0.53-0.98, p = <0.05, I2 = 49%, n = 4 studies; GG vs. (GT + TT): OR = 0.73, 95% CI = 0.55-0.96, p = <0.05, I2 = 44%, n = 4 studies. No significant association was observed between the rs2241766 polymorphism and the DR risk. Conclusions: The current meta-analysis supports the association between the rs1501299 polymorphism of the ADIPOQ gene and the DR risk in patients with DM.

Autistic spectrum disorder (ASD) is a neurodevelopmental disability characterised by the impairment of social interaction and communication ability. The alarming increase in its prevalence in children urged researchers to obtain a better understanding of the causes of this disease. Genetic factors are considered to be crucial, as ASD has a tendency to run in families. In recent years, with technological advances, the importance of structural variations (SVs) in ASD began to emerge. Most of these studies, however, focus on the Caucasian population. As a populated ethnicity, ASD shall be a significant health issue in China. This systematic review aims to summarise current case-control studies of SVs associated with ASD in the Chinese population. A list of genes identified in the nine included studies is provided. It also reveals that similar research focusing on other genetic backgrounds is demanded to manifest the disease etiology in different ethnic groups, and assist the development of accurate ethnic-oriented genetic diagnosis.

BACKGROUND: Alexithymia is a trait involving difficulties in processing emotions. Genetic association studies have investigated candidate genes involved in alexithymia\'s pathogenesis. Therefore, the aim of the present study was to perform a systematic review of the genetic background associated with alexithymia.
METHODS: A systematic review of genetic studies of people with alexithymia was conducted. Electronic databases including PubMed, Scopus, and Web of Science were searched for the study purpose. We used the words \"Alexithymia\", \"gene\", \"genetics\", \"variants\", and \"biomarkers\". The present systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We found only candidate gene studies. A total of seventeen studies met the eligibility criteria, which comprised 22,361 individuals. The candidate genes associated with alexithymia were the serotoninergic pathway genes solute carrier family 6 member 4 (SLC6A4), serotonin 1A receptor (HTR1A), and serotonin 1A receptor (HTR2A); the neurotransmitter metabolism genes dopamine receptor D2 (DRD2), ankyrin repeat and kinase domain containing 1 (ANKK1), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and oxytocin receptor (OXTR); and other pathway genes, vitamin D-binding protein (VDBP), tumor protein P53 regulated apoptosis inducing protein 1 (TP53AIP1), Rho GTPase Activating Protein 32 (ARHGAP32), and transmembrane protein 88B (TMEM88B).
CONCLUSIONS: The results of this study showed that only case-control gene studies have been performed in alexithymia. On the basis of our findings, the majority of alexithymia genes and polymorphisms in this study belong to the serotoninergic pathway and neurotransmitter metabolism genes. These data suggest a role of serotoninergic neurotransmission in alexithymia. Nevertheless, more and future research is required to learn about the role of these genes in alexithymia.

Maturity-onset diabetes of the young (MODY) represents the most frequent form of monogenic diabetes mellitus (DM), currently classified in 14 distinct subtypes according to single gene mutations involved in the differentiation and function of pancreatic β-cells. A significant proportion of MODY has unknown etiology, suggesting that the genetic landscape is still to be explored. Recently, novel potentially MODY-causal genes, involved in the differentiation and function of β-cells, have been identified, such as RFX6, NKX2.2, NKX6.1, WFS1, PCBD1, MTOR, TBC1D4, CACNA1E, MNX1, AKT2, NEUROG3, EIF2AK3, GLIS3, HADH, and PTF1A. Genetic and clinical features of MODY variants remain highly heterogeneous, with no direct genotype-phenotype correlation, especially in the low-penetrant subtypes. This is a narrative review of the literature aimed at describing the current state-of-the-art of the novel likely MODY-associated variants. For a deeper understanding of MODY complexity, we also report some related controversies concerning the etiological role of some of the well-known pathological genes and MODY inheritance pattern, as well as the rare association of MODY with autoimmune diabetes. Due to the limited data available, the assessment of MODY-related genes pathogenicity remains challenging, especially in the setting of rare and low-penetrant subtypes. In consideration of the crucial importance of an accurate diagnosis, prognosis and management of MODY, more studies are warranted to further investigate its genetic landscape and the genotype-phenotype correlation, as well as the pathogenetic contribution of the nongenetic modifiers in this cohort of patients.

OBJECTIVE: Alcohol drinking is a major risk factor for head and neck cancer (HNC), and this risk may be modified by alcohol dehydrogenase (ADH) genes. The first systematic review and meta-analysis was designed with more studies and added trial sequential analysis and functional analysis for a better understanding of the role of ADH3 polymorphism in HNC patients.
METHODS: A search was performed across several databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up to May 5, 2024, without any restrictions to find pertinent studies. The RevMan 5.3 software was used to calculate the effect sizes. These were expressed as the odds ratio (OR) with a 95 % confidence interval.
RESULTS: Twenty-seven articles were included in the meta-analysis. The frequency of *1/*1, *1/*2, and *2/*2 genotypes in cases with HNC was 47.14 %, 41.06 %, and 11.80 %, respectively, and in controls was 50.56 %, 38.29 %, and 11.15 %, respectively. The pooled OR for the allelic model is 1.11 (p = 0.18), for the homozygous model is 0.95 (p = 0.64), for the heterozygous model is 0.99 (p = 0.90), for the dominant model is 1.11 (p = 0.14), and for the recessive model is 0.98 (p = 0.78). In the Asians, the three models showed an increased significant association. In the cancer subtype subgroup, a protective significant association was found in the pharyngeal cancer subtype.
CONCLUSIONS: The current analysis suggests that ADH3 polymorphism may not have a significant impact on the risk of HNC, but the polymorphism had an increased risk in Asians and a protective role in pharyngeal cancers.

BACKGROUND: Biallelic variants in thiamine pyrophosphokinase 1 ( TPK1 ) are known to cause thiamine metabolism dysfunction syndrome 5 (THMD5). This disorder is characterized by neuroregression, ataxia and dystonia with basal ganglia abnormalities on neuroimaging. To date, 27 families have been reported with THMD5 due to variants in TPK1 .
METHODS: We ascertained three individuals from three unrelated families. Singleton exome sequencing was performed on all three individuals, followed by in silico mutagenesis of the mutant TPK protein. Additionally, we reviewed the genotypic and phenotypic information of 27 previously reported individuals with THMD5.
RESULTS: Singleton exome sequencing revealed a novel homozygous variant c.620A>T p.(Asp207Val) in TPK1 (NM_022445.4) in all three individuals. In silico mutagenesis of the mutant protein revealed a decrease in protein stability and altered interactions with its neighboring residues compared to the wild-type protein. Thus, based on strikingly similar clinical and radiological findings compared to the previously reported individuals and with the support of in silico mutagenesis findings, the above-mentioned variant appears to be the probable cause for the condition observed in the affected individuals in this study.
CONCLUSIONS: We report a novel homozygous variant in TPK1 , which appears to be recurrent among the Indian population.