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BACKGROUND: It is unclear whether brief interventions using the combined classification of alcohol-metabolizing enzymes aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) together with behavioral changes in alcohol use can reduce excessive alcohol consumption. This study aimed to examine the effects of a brief intervention based on the screening of ALDH2 and ADH1B gene polymorphisms on alcohol consumption in Japanese young adults.
METHODS: In this open-label randomized controlled trial, we enrolled adults aged 20-30 years who had excessive drinking behavior (average amount of alcohol consumed: men, ≥  4 drinks/per day and women, ≥  2 drinks/per day; 1 drink = 10 g of pure alcohol equivalent). Participants were randomized into intervention or control group using a simple random number table. The intervention group underwent saliva-based genotyping of alcohol-metabolizing enzymes (ALDH2 and ADH1B), which were classified into five types. A 30-min in-person or online educational counseling was conducted approximately 1 month later based on genotyping test results and their own drinking records. The control group received traditional alcohol education. Average daily alcohol consumption was calculated based on the drinking diary, which was recorded at baseline and at 3 and 6 months of follow-up. The primary endpoint was average daily alcohol consumption, and the secondary endpoints were the alcohol-use disorder identification test for consumption (AUDIT-C) score and behavioral modification stages assessed using a transtheoretical model.
RESULTS: Participants were allocated to the intervention (n = 100) and control (n = 96) groups using simple randomization. Overall, 28 (29.2%) participants in the control group and 21 (21.0%) in the intervention group did not complete the follow-up. Average alcohol consumption decreased significantly from baseline to 3 and 6 months in the intervention group but not in the control group. The reduction from baseline alcohol consumption values and AUDIT-C score at 3 months were greater in the intervention group than in the control group (p < 0.001). In addition, the behavioral modification stages were significantly changed by the intervention (p < 0.001).
CONCLUSIONS: Genetic testing for alcohol-metabolizing enzymes and health guidance on type-specific excessive drinking may be useful for reducing sustained average alcohol consumption associated with behavioral modification.
BACKGROUND: R000050379, UMIN000044148, Registered on June 1, 2021.

BACKGROUND: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status.
OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR).
METHODS: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs.
RESULTS: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes.
CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

BACKGROUND: Cognitive decline, and more specifically Alzheimer\'s disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids.
OBJECTIVE: We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual\'s genetically conferred risk of cognitive decline.
METHODS: The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness).
RESULTS: Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits.
CONCLUSIONS: In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disease with a high disability rate, and genetic factors are closely related to its pathogenesis. This study aimed to investigate the possible correlation between ESR1 and APOE gene polymorphisms and the risk of ONFH.
METHODS: In this case-control study, the potential association between three genetic variants (rs2982573 C < T, rs10872678 C < T, and rs9322332 A < C) of the ESR1 gene and two genetic variants (rs7259620 A < G and rs769446 C < T) of the APOE gene with the risk of ONFH was investigated. Correlations between gene polymorphisms and ONFH risk were assessed using logistic regression analysis, with calculation of odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: The overall analysis demonstrated that rs9322332 in the ESR1 gene exhibited a correlation with a decreased risk of ONFH under the homozygous (AA vs.CC: OR = 0.69, 95% CI [0.53-0.90], p = 0.006), dominant (CA + AA vs. CC: OR = 0.70, 95% CI [0.54-0.90], p = 0.006), and additive (OR = 0.79, 95% CI [0.66-0.95], p = 0.013) models. The stratification analysis revealed that rs9322332 was linked to a lower risk of ONFH in subgroups characterized by individuals aged over 51 years and non-smokers. Nevertheless, there were no notable correlations found between ESR1 rs2982573 and rs10872678, as well as APOE rs7259620 and rs769446, with the risk of ONFH.
CONCLUSIONS: ESR1-rs9322332 is closely linked to a decreased risk of ONFH, thereby enhancing our understanding of the relationship between gene polymorphisms and ONFH.

Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and -420C>G polymorphisms in the resistin gene with AAA susceptibility and progression.
We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and -420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders.
The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of -420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of -420C>G polymorphism were found to be associated with an increased risk and progression of AAA.
The -420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

Background: Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Conclusion: Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.

A systematic review and meta-analysis is a useful method to summarize the different results from primary data, which can then provide an evidence-based outcome. Meta-analysis generates quantitative data by calculating effect sizes, which include odd ratios, relative risks, proportions, correlation coefficients, and so forth. The study of single-nucleotide polymorphisms (SNPs) and the association with the interested outcome is one discipline that has resulted in inconsistent relations. Therefore, the meta-analysis aimed to summarize the relevant data on SNPs associated with the outcome of interest. Herein, we describe a comprehensive meta-analysis on Toll-like receptor-9 polymorphism and the risk of cervical cancer.

UNASSIGNED: Colorectal cancer (CRC) is the third most common malignant tumor in the world. The morbidity and mortality rates in Western countries have decreased, but they are still on the rise in China. C10orf90 is associated with a variety of cancers, but the correlation between C10orf90 and CRC is not yet known.
UNASSIGNED: A total of 1,339 subjects were randomly enrolled in our study. After extracting their DNA, three single-nucleotide polymorphisms (SNPs) of C10orf90 were genotyped to analyze the potential relationship between these variants and CRC risk. PLINK software packages (version 1.07) were used to evaluate multiple genetic models by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The best SNP-SNP interaction model was defined by the multifactor dimensionality reduction (MDR) analysis.
UNASSIGNED: C10orf90 rs12412320 was significantly associated with CRC risk (p = 0.006) and might be associated with the lower CRC risk (OR: 0.78; 95% CI: 0.65-0.93). The relationship of rs12412320 with lower CRC risk was found in people aged >60 years and ≤60 years, women, non-smokers, or non-drinkers. Rs11245008 in people aged ≤60 years and rs11245007 among men had a higher CRC susceptibility. Rs12412320 was related to the lower risk of advanced stages (III/IV stage), while rs11245007 might be associated with the higher risk of advanced stages (III/IV stage). Moreover, rs12412320 had the most significant relationship with the susceptibility to rectal cancer.
UNASSIGNED: This study is the first to report between C10orf90 gene polymorphisms and CRC risk in Chinese people, which suggests that C10orf90 rs12412320 might play a crucial role in preventing CRC occurrence.

UNASSIGNED: Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL).
UNASSIGNED: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test.
UNASSIGNED: In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003).
UNASSIGNED: A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.