Evaluation of the Modified SAMe-TT2R2 Score to Predict Good Anticoagulation Control with Warfarin Among non-valvular Atrial Fibrillation Patients

Background: The SAMe-TT2 R2 Score was developed to identify vitamin K antagonists control outliers before non-valvular atrial fibrillation (AF) patients start treatment. SAMe-TT2 R2 Score was derived and validated using a primarily white Caucasian population to predict TTR. Given that non-Caucasian race already confers 2 points in this score, the SAMe-TT2 R2 score requires validation and/or re-calibration despite race of population. Method: We conducted a cohort retrospective study that included all non-valvular atrial fibrillation patients who were on warfarin therapy from January to December 2019. Then we calculated the modified SAMe-TT2 R2 and SAMe-TT2 R2 for all study populations and we correlated the result with patients' TTR. The TTR was calculated through the Rosendaal's method. Results: We had 662 patient using warfarin therapy, among those 662, 60.9% were under cardiology and using it for cardiac indication, and only 18.1% diagnosed to have non-valvular AF. Modified SAMe-TT2 R2 score has good relation to original SAMe-TT2 R2 score as showed 75.71% (95% CI. 63.99 to 85.17%), 100% (95% CI. 92.89 to 100%) and 15% (95% CI. 3.21 to 77.95%); accuracy, sensitivity and specificity in relation to SAMe-TT2 R2 respectively. In addition to that in this small cohort we found that there is universal relationship between SAMe-TT2 R2 score, Modified SAMe-TT2 R2 score and TTR; TTR >=65% associate with low score (<2) of both SAMe-TT2 R2 , Modified SAMe-TT2 R2 score. Conclusion: The use of Modified SAMe-TT2 R2 score allows clinicians to make an informed decision on whether to start vitamin K antagonist or other non-vitamin K antagonist oral anticoagulant despite the race of the patients.

The Associations between Interleukin-17 Single Nucleotide Polymorphism and Colorectal Cancer Susceptibility: A Systematic Review and Meta-Analysis

Backgrounds: Numerous of case-control studies have reported the associations between Interleukin-17 (IL-17) polymorphisms and colorectal cancer, however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility.Materials and method: Relevant Studies were extracted from electronic databases of Pubmed, Embase, Web of science, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CMB) up to April 2021. The Odds ratio and 95% confidence interval were conducted to estimate the strength of the associations and the Stata 13.0 software was used to perform the meta-analysis.Results: Ten articles including 2599 cases and 2845 controls were enrolled in our research after strictly literature screening. Highly significant associations between IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all the five gene models (allelic, dominant, recessive, homozygous and heterozygous models), subgroup analysis based on ethnicity revealed that these associations existed not only in Asia population, but also in Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated to IL-17F rs763780 polymorphism and a slightly lower colorectal cancer susceptibility for Caucasian population was discovered in the recessive and homozygous models of this mutation.Conclusion: IL-17A rs2275913 polymorphism may be an independent risk factor contributed to colorectal cancer susceptibility, while IL-17F rs763780 polymorphism displayed a possible decreased susceptibility to colorectal cancer. Future studies with large-scale samples were warranted to identify these associations.

Filaggrin gene polymorphisms are associated with atopic dermatitis in women but not in men in the Caucasian population of Central Russia

Background and purpose This study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia. Methods The study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females. Results Significant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19–2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18–2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology. Conclusion Polymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia.

Association of Insulin Resistance with Vascular Ageing in a General Caucasian Population: An EVA Study

The data on the relationship between insulin resistance and vascular ageing are limited. The aim of this study was to explore the association of different indices of insulin resistance with vascular ageing in an adult Caucasian population without cardiovascular disease. We selected 501 individuals without cardiovascular disease (mean age: 55.9 years, 50.3% women) through random sampling stratified by sex and age. Arterial stiffness was evaluated by measuring the carotid-to-femoral pulse wave velocity (cfPWV) and brachial-to-ankle pulse wave velocity (baPWV). The participants were classified into three groups according to the degree of vascular ageing: early vascular ageing (EVA), normal vascular ageing (NVA) and healthy vascular ageing (HVA). Insulin resistance was evaluated with the homeostatic model assessment of insulin resistance (HOMA-IR) and another five indices. The prevalence of HVA and EVA was 8.4% and 21.4%, respectively, when using cfPWV, and 7.4% and 19.2%, respectively, when using baPWV. The deterioration of vascular ageing, with both measurements, presented as an increase in all the analysed indices of insulin resistance. In the multiple regression analysis and logistic regression analysis, the indices of insulin resistance showed a positive association with cfPWV and baPWV and with EVA.

The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis

MUC5B promoter rs35705950 T/G gene polymorphism has been associated with the risk of IPF, but the influence of this relationship varies among different populations. In the past 2 years, there were new clinical studies with different results, but none of them reached unified conclusions. Therefore, this study further included the latest case–control studies, integrated their results and carried out meta-analysis on them to draw reliable conclusions. PubMed, EMBASE, CNKI, Wanfang database and VIP Chinese science were searched by a computer to collect the related literatures of MUC5B gene polymorphism and IPF susceptibility published before June 15, 2021. The first author, year of publication, diagnostic criteria and gene frequency were extracted after screened them. Forest plot was drawn and the trial sequential analysis (TSA) was carried out to confirm the stability of the meta-analysis results. Registration number: CRD42021272940. A total of 24 case–control studies (13 studies on the Caucasian, 7 studies on the Asian and 4 studies on the mixed population), and a total of 6749 IPF patients and 13,898 healthy controls were included in this study. The T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B promoter rs35705950 T/G polymorphism were associated with IPF risk in all populations, and the effect values were ([OR] 4.12, 95% CI [3.64, 4.67]), ([OR] 10.12, 95% CI [7.06, 14.49]), ([OR] 4.84, 95% CI [3.85, 6.08]), ([OR] 4.84, 95% CI [3.79, 6.19]) and ([OR] 5.11, 95% CI [4.02, 6.49]), respectively. The results of TSA confirmed the stability of the results. Subgroup analysis showed that T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B polymorphism were associated with IPF risk in Caucasian population. The effect values were ([OR] 4.50, 95% CI [3.93, 5.16]), ([OR] 10.98, 95% CI [7.59, 15.89]), ([OR] 6.27, 95% CI [5.37, 7.32]), ([OR] 6.30, 95% CI [5.19, 7.64]) and ([OR] 5.15, 95% CI [4.01, 6.61]), respectively. Similar results were also found in Asian and mixed populations. The association strength of the minor T allele in the Caucasian was more significant than that of the Asian population ([OR] 4.50 vs. [OR] 2.39), and the association strength of all genetic models carrying "T" was more significant than that of the Asian population ([OR] 10.98 vs. [OR] 4.29). In Caucasian, Asian and mixed populations, T minor allele carriers were more likely to be susceptible to pulmonary fibrosis, and TT genotype carriers were more likely to be susceptible to IPF than GT genotype carriers. The association between IPF and Caucasian population with minor T allele and all "T" genetic model was more significant than that of Asian population.

Association of Adenosine Deaminase (ADA) +22 G->A (rs73598374) Genotype in Latino Adult Obese

Obesity is a health burden that currently affects over 13% of the global adult population, consisting of over 650 million adults. Obesity is evaluated based on a body mass index (BMI) scale, which is calculated as weight in kilograms divided by the square of height in meters. Adults with a BMI greater than 30kg/m2 are considered to be obese while adults with a BMI greater than 40kg/m2 are considered morbidly obese. Adenosine deaminase (ADA) is a polymorphic enzyme that plays an important role in both immune functions and the regulation of intracellular and extracellular concentrations of adenosine. Three alleles of the ADA gene (ADA1, ADA2, ADA6) are associated with type 1 diabetes mellitus (DM1). ADA2/6 may increase susceptibility to DM1 in females. Given the evidence linking obesity with DM1, we wanted to determine whether a correlation exists between ADA2 allele and obesity. The ADA2 (+22 G->A, rs73598374) SNP changes the amino acid at position 8 from aspartic acid (Asp8)(D) to asparagine (Asn)(N). In this study, we present significant evidence of association between the ADA2 allele and obesity or BMIs greater than 25 in the Latino adult but not in the Caucasian population and therefore, may be a risk for obesity and its complications such as DM1.