UNASSIGNED: This study aimed to explore genetic variations associated with DNA repair mechanisms to enhance the management of both oral cancer (OC) and oral precancer (OPC).
UNASSIGNED: A cohort of 380 patients diagnosed with OC and OPC, comprising 220 males and 160 females, was analyzed. Participants were categorized based on their tobacco-chewing habits, with corresponding control groups established. Key genetic markers investigated for polymorphisms included OGG1, APE1, and XRCC1.
UNASSIGNED: The XRCC1 Arg280H variant demonstrated significant associations with the susceptibility to both OC and OPC across various models. Further analyses, incorporating factors such as tobacco and alcohol consumption, unveiled a correlation between the XRCC1 Arg194Trp variant and an elevated risk of developing head and neck cancer. Stratified analyses also revealed an increased risk of OC or OPC based on the specific site of the cancer.
UNASSIGNED: The study underscores the importance of XRCC1 polymorphisms, particularly XRCC1 Arg280H and XRCC1 Arg194Trp, within the genetic framework of OC and OPC. Understanding these genetic associations provides valuable insights for the potential development of targeted interventions aimed at individuals predisposed to these conditions.

UNASSIGNED: Fibroblast growth factors (FGFs) play a key role in embryo implantation and support endometrial trophoblastic interaction.
UNASSIGNED: The aim of the study was to evaluate the association between FGF-1 (rs34011) gene variety and its serum concentration with repeated implantation failure (RIF).
UNASSIGNED: The design of the study was a cross-sectional study.
UNASSIGNED: Four hundred infertile women with a history of RIF and 400 healthy women undergoing the first in vitro fertilisation-embryo transfer attempt with successful delivery (controls) were enrolled in the study. Genomic DNA was extracted from peripheral blood leucocytes and genotyped by Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction. Serum FGF-1 concentration was evaluated with enzyme-linked immunosorbent assay.
UNASSIGNED: The ANOVA test was used to analyse the difference between the means of the groups.
UNASSIGNED: In RIF group, the genotype frequencies of the GG, GA and AA were 59%, 33.5% and 7.5%, respectively, whereas in controls were 72.5%, 24% and 3.5%, respectively. The G and A allele frequencies in the RIF group were 75.75% and 24.25%, while in controls were 84.5% and 15.5%, respectively (P < 0.0001). We have also shown that serum FGF-1 concentration in RIF and control groups was 17 ± 3.55 and 23.62 ± 4.91 pg/mL, respectively (P = 0.008). We have also shown that AA genotype is significantly associated with decreased serum FGF-1 concentration in RIF (AA, GA and GG serum levels were 9.55 ± 2.65, 14 ± 3.35 and 22.55 ± 7.26 pg/mL, and in controls were 12.22 ± 2.27, 18.44 ± 5.98 and 26.66 ± 8.29 pg/mL, respectively).
UNASSIGNED: The current study suggests that a significant association between FGF-1 (rs34011) promoter polymorphism and its serum concentration with RIF. The study also suggests that AA genotype is linked to lower FGF-1 serum levels and may play a risk factor for RIF.

The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. The work in the manuscript leveraged 4 publicly available datasets to investigate the mechanism by which rs11573156 influences sPLA2-IIA levels via bioinformatics and modeling analysis. Through genotype-tissue expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS was used to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified eQTL SNPs. Subsequently, candidate TF-SNP interactions were cross-referenced with the ChIP-seq results in matched tissues from ENCODE. SP1-rs11573156 emerged as the significant TF-SNP pair in the liver. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was likely affected by tissue SP1 protein levels. Using an ordinary differential equation based on Michaelis-Menten kinetic assumptions, we modeled the dependence of PLA2G2A transcription on SP1 protein levels, incorporating the SNP influence. Collectively, our analysis strongly suggests that the difference in the binding dynamics of SP1 to different rs11573156 alleles may underlie the allele-specific PLA2G2A expression in different tissues, a mechanistic model that awaits future direct experimental validation. This mechanism likely contributes to the variation in circulating sPLA2-IIA protein levels in the human population, with implications for a wide range of human diseases.

(1) Background: This study was aimed to identify universal genetic markers of multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) and establish statistical associations among identified mutations to enhance understanding of MDR in Mtb and inform diagnostic and treatment development. (2) Methods: GWAS analysis and the statistical evaluation of identified polymorphic sites within protein-coding genes of Mtb were performed. Statistical associations between specific mutations and antibiotic resistance were established using attributable risk statistics. (3) Results: Sixty-four polymorphic sites were identified as universal markers of drug resistance, with forty-seven in PE/PPE regions and seventeen in functional genes. Mutations in genes such as cyp123, fadE36, gidB, and ethA showed significant associations with resistance to various antibiotics. Notably, mutations in cyp123 at codon position 279 were linked to resistance to ten antibiotics. The study highlighted the role of PE/PPE and PE_PGRS genes in Mtb\'s evolution towards a \'mutator phenotype\'. The pathways of acquisition of mutations forming the epistatic landscape of MDR were discussed. (4) Conclusions: This research identifies marker mutations across the Mtb genome associated with MDR. The findings provide new insights into the molecular basis of MDR acquisition in Mtb, aiding in the development of more effective diagnostics and treatments targeting these mutations to combat MDR tuberculosis.

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups.

Roles of genes in heat acclimation (HA, repeated exercise-heat exposures) had not been explored. ACE I/D and ACTN3 R577X genetic polymorphisms are closely associated with outstanding exercise performances. This study investigated whether the two polymorphisms influenced the response to HA. Fifty young Han nationality male subjects were selected and conducted HA for 2 weeks. Exercise indicators (5-km run, push-up and 100-m run) were tested and rest aural thermometry (RTau) was measured before and after HA. ACE gene was grouped by I homozygote and D carrier, and ACTN3 gene was grouped by R homozygote and X carrier. Results showed that there were no differences between groups in age, body mass index, exercise indicators and RTau before HA. After HA, RTau of ACE I homozygote was lower than that of D carrier [F (1, 48) = 9.12, p = 0.004, η = 0.40]. Compared with RTau before HA, that of I homozygote decreased after HA (Δ = -0.26 °C, 95 % CI -0.34-0.18, p < 0.001), while that of D carrier did not change. There was a ACE gene × HA interaction in RTau [F (1, 48) = 14.26, p < 0.001, η = 0.48]. No effect of ACTN3 gene on RTau was observed. For exercise indicators, there were no differences between groups after HA, and no gene × HA interactions were observed. There may be a strong interaction of ACE gene and HA in the change of rest core temperature. I homozygote may have an advantage on improving heat tolerance.

OBJECTIVE: Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1, XRCC2, XRCC3, and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility.
METHODS: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05).
RESULTS: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population.
CONCLUSIONS: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.

UNASSIGNED: Genetic association studies can reveal biology and treatment targets but have received limited attention for stroke recovery. STRONG (Stroke, Stress, Rehabilitation, and Genetics) was a prospective, longitudinal (1-year), genetic study in adults with stroke at 28 US stroke centers. The primary aim was to examine the association that candidate genetic variants have with (1) motor/functional outcomes and (2) stress-related outcomes.
UNASSIGNED: For motor/functional end points, 3 candidate gene variants (ApoE ε4, BDNF [brain-derived neurotrophic factor], and a dopamine polygenic score) were analyzed for associations with change in grip strength (3 months-baseline), function (3-month Stroke Impact Scale-Activities of Daily Living), mood (3-month Patient Health Questionnaire-8), and cognition (12-month telephone-Montreal Cognitive Assessment). For stress-related outcomes, 7 variants (serotonin transporter gene-linked promoter region, ACE [angiotensin-converting enzyme], oxytocin receptor, FKBP5 [FKBP prolyl isomerase 5], FAAH [fatty acid amide hydrolase], BDNF, and COMT [catechol-O-methyltransferase]) were assessed for associations with posttraumatic stress disorder ([PTSD]; PTSD Primary Care Scale) and depression (Patient Health Questionnaire-8) at 6 and 12 months; stress-related genes were examined as a function of poststroke stress level. Statistical models (linear, negative binomial, or Poisson regression) were based on response variable distribution; all included stroke severity, age, sex, and ancestry as covariates. Stroke subtype was explored secondarily. Data were Holm-Bonferroni corrected. A secondary replication analysis tested whether the rs1842681 polymorphism (identified in the GISCOME study [Genetics of Ischaemic Stroke Functional Outcome]) was related to 3-month modified Rankin Scale score in STRONG.
UNASSIGNED: The 763 enrollees were 63.1±14.9 (mean±SD) years of age, with a median initial National Institutes of Health Stroke Scale score of 4 (interquartile range, 2-9); outcome data were available in n=515 at 3 months, n=500 at 6 months, and n=489 at 12 months. At 1 year poststroke, the rs6265 (BDNF) variant was associated with poorer cognition (0.9-point lower telephone-Montreal Cognitive Assessment score, P=1×10-5). For stress-related outcomes, rs4291 (ACE) and rs324420 (FAAH) were risk factors linking increased poststroke stress with higher 1-year depression and PTSD symptoms (P<0.05), while rs4680 (COMT) linked poststroke stress with lower 1-year depression and PTSD. Findings were unchanged when considering stroke subtype. STRONG replicated GISCOME: rs1842681 was associated with lower 3-month modified Rankin Scale score (P=3.2×10-5).
UNASSIGNED: This study identified genetic associations with cognitive function, depression, and PTSD 1 year poststroke. Genetic susceptibility to PTSD and depressive symptoms varied according to the amount of poststroke stress, underscoring the critical role of lived experiences in recovery. Together, the results suggest that genetic association studies provide insights into the biology of stroke recovery in humans.

UNASSIGNED: Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN.
UNASSIGNED: A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines.
UNASSIGNED: The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT, DRD2, DRD3, and DAT1, regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN.
UNASSIGNED: There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder.Systematic review registration: [https://clinicaltrials.gov/], identifier [CRD42023452548].

Malaria is still a public health problem in tropical countries like India; major malaria parasite species are Plasmodium falciparum and P. vivax. Of which, P. vivax is responsible for ∼40% of the malaria burden at least in the Indian scenario. Unfortunately, there is limited data on the population structure and genetic diversity of P. vivax parasites in India. In this study, we investigated the genetic diversity of P. vivax strains in the South-west district, Delhi and, Nuh district, Haryana [National Capital Region (NCR)], using a polymorphic marker- P. vivax merozoite surface protein-3α (PvMSP-3α) gene. Dried blood spots from microscopically confirmed P. vivax patients were used for investigation of the PvMSP-3α gene. PCR-RFLP was performed on the PvMSP-3α gene to investigate the genotypes and allelic variability with HhaI and AluI restriction enzymes. In total, 40 successfully PCR amplified PvMSP-3α gene segments were subjected to RFLP analysis. Amplified products showed three different base pair size variations viz. genotype A in 31(77.5%), genotype B in 4(10%) and genotype C in 5(12.5%) P. vivax specimens. RFLP with HhaI and AluI revealed 17 (H1-H17) and 25 (A1-A25) allelic variants, respectively. Interestingly, two similar sub-allelic variants, ie. H8 (with HhaI), and A4 (with AluI) clustered within the rural area of Nuh district, Haryana in two samples. With this study, we propose to commission such type of genetic diversity analysis of P. vivax to investigate the circulating genotypes of the parasites from distinct geographical locations across India, that can have significant implications in understanding the population structures of P. vivax.