Association study of genetic variants at TTC32‐WDR35 gene cluster with coronary artery disease in Chinese Han population

BackgroundTTC32‐WDR35 gene cluster has been genome‐wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.MethodsWe performed a case‐control study enrolling 935 CAD cases and 935 age‐sex‐frequency‐matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.ResultsThis study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54‐0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42‐0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.ConclusionsSNP rs721932 at TTC32‐WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.     

TLR4 polymorphisms as potential predictors of atopic dermatitis in Chinese Han children

BackgroundToll‐like receptor 4 (TLR4) is considered to be involved in the pathogenesis and progression of atopic dermatitis (AD). In the present study, we evaluated the relationship between TLR4 gene polymorphisms and the susceptibility or severity of AD among Chinese Han children.MethodsA total of 132 AD patients and 100 healthy controls were enrolled in this study. Four single‐nucleotide polymorphisms (rs19277914, rs11536891, rs7869402, and rs11536889) of the TLR4 gene were genotyped by multiplex PCR combined with next‐generation sequencing.ResultsOur results showed that a significantly reduced risk for AD was associated with C allele [p = 0.008; odds ratio (OR) = 0.41, C vs. T], TC genotype (p = 0.022; OR = 0.41, TC vs. TT), and TC + CC genotype (p = 0.010; OR = 0.39, TC + CC vs. TT) of TLR4 rs11536891. The frequency of the haplotype GCCG (rs1927914–rs11536891–rs7869402–rs11536889) in AD patients was lower than that in the controls (p = 0.010; OR = 0.38). Moreover, the results indicated that a higher risk of severe AD was related to the T allele (p = 0.019; OR = 2.97, T vs. C) and the TC genotype (p = 0.021; OR = 3.34, TC vs. CC) of TLR4 rs7869402. A risk haplotype of TLR4 (GTTG) was found in severe AD patients (p = 0.010; OR = 5.26).ConclusionsOur data suggested that TLR4 rs11536891 polymorphism was associated with the susceptibility to AD in Chinese Han children. And TLR4 rs7869402 might confer the severity of pediatric AD patients.     

Neutrophil percentage‐to‐albumin ratio and monocyte‐to‐lymphocyte ratio as predictors of free‐wall rupture in patients with acute myocardial infarction

BackgroundsFree‐wall rupture (FWR) has a high mortality rate. We aimed to find sensitive predictive indicators to identify high‐risk FWR patients by exploring the predictive values of neutrophil percentage‐to‐albumin ratio (NPAR) and monocyte‐to‐lymphocyte ratio (MLR) on patients with acute myocardial infarction (AMI).Methods76 FWR patients with AMI were collected, and then 228 non‐CR patients with AMI were randomly selected (1:3 ratio) in this retrospective study. The independent influencing factors of FWR were evaluated by univariate and multivariate logistic regression analysis. The receiver‐operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of NPAR and MLR for FWR.ResultsAccording to the results of multivariate logistic regression analysis, emergency percutaneous coronary intervention (PCI) (OR = 0.27, 95% CI: 0.094–0.751, p = 0.012), angiotensin‐converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) treatment (OR = 0.17, 95% CI: 0.044–0.659, p = 0.010), NPAR (OR = 2.69, 95% CI: 1.031–7.044, p = 0.043), and MLR (OR = 5.99, 95% CI: 2.09–17.168, p = 0.001) were the influencing factors of the FWR patients with AMI, independently. Additionally, the NPAR and MLR were the predictors of FWR patients, with AUC of 0.811 and 0.778, respectively (both p < 0.001).ConclusionsIn summary, the emergency PCI and ACEI/ARB treatment were independent protective factors for FWR patients with AMI, while the increase of MLR and NPAR were independent risk factors. What''s more, NPAR and MLR are good indicators for predicting FWR.     

Association of ANGPTL3 polymorphisms with high‐density lipoprotein cholesterol uptake capacity in patients with cardiovascular disease

IntroductionPrevious studies have shown the importance of angiopoietin‐like 3 (ANGPTL3) as a modulator of lipid profiles. Cholesterol uptake capacity (CUC) is one means for assessing high‐density lipoprotein (HDL) functionality. This study for the first time has investigated the relationship between genetic ANGPTL3 polymorphism and CUC in patients with cardiovascular disease.MethodsFive hundred three subjects comprising 350 healthy subjects and 153 individuals who developed a cardiovascular disease (CVD) event during follow‐up were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. A modified CUC method was used to determine the CUC of serum samples. Applied amplification refractory mutation system PCR was performed for ANGPTL3 variants genotyping including: rs10789117, rs1748195, and rs11207997. Sanger sequencing was applied to confirm the genotypes.ResultsThe results showed that there was a significant relationship between the rs1748195 genotypes and HDL concentration in the CVD group (p = 0.02). Moreover, individuals with a GG genotype of the rs1748195 were associated with a lower risk of CVD (OR = 0.49, 95% CI = 0.24–0.98, p = 0.04) compared with CC genotype in the CUC ≤ 1.7 a.u subgroup. Moreover, the CT genotype of rs11207997 was associated with a lower risk of CVD (OR = 0.74, 95% CI = 0.41–1.3, p = 0.01) compared with CC genotype in CUC > 1.7 a.u subgroup.ConclusionThe results showed that the CT genotype of the rs11207997 variant was associated with a lower risk of incident CVD in patients with higher HDL functionality. As well, the rs1748195 gene variant may contribute to a reduced risk of CVD.     

Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.MethodsThe CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.ResultsA higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed.ConclusionThe CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.     

The relationship between vitamin D receptor gene and TREM‐1 gene polymorphisms and the susceptibility and prognosis of neonatal sepsis

ObjectiveThe objective of this was to study the relationship between vitamin D receptor (VDR) and triggering receptor expressed on myeloid cells 1 (TREM‐1) gene single‐nucleotide polymorphisms (SNP) and neonatal sepsis susceptibility and prognosis.MethodsThe blood of 150 neonatal sepsis patients and 150 normal neonates was collected, and genomic DNA was extracted. Sanger sequencing was used to analyze the genotypes of VDR rs739837 and TREM‐1 rs2234246.ResultsVitamin D receptor rs739837 locus GT, TT genotype, dominant model, and recessive model were all protective factors for sepsis (0 < OR < 1, p < 0.05). The risk of sepsis in carriers of the rs739837 G allele was 0.65 times that of the rs739837 T allele (95% CI: 0.50–0.83, p < 0.001), CT, TT, dominant model, and recessive model at rs2234246 were risk factors for sepsis (OR > 1, p < 0.05). The risk of sepsis in carriers of the rs739837 T allele was 1.38 times that of carriers of the C allele (95% CI: 1.16–1.61, p < 0.001). The polymorphisms of VDR gene rs739837 and TREM‐1 gene rs2234246 were not significantly correlated with the survival of patients with neonatal sepsis (p > 0.05).Conclusion Vitamin D receptor gene rs739837 locus G>T is associated with a reduction in the risk of neonatal sepsis, TREM‐1 rs2234246 C>T is associated with the increased risk of neonatal sepsis, but none of them was significantly associated with the prognosis of neonatal sepsis.     

Association of polymorphisms in the IL‐10 promoter region with Crohn's disease

BackgroundIL‐10 is thought to play an important role in preventing inflammatory bowel disease (IBD), although its efficacy is limited in IBD inflammation treatment. The purpose of this study is to investigate the association between SNP polymorphism in the promoter region of the IL‐10 gene and Crohn''s disease (CD).MethodsIn 86 children with CD disease and 142 healthy controls, polymorphisms of three SNPs (rs3790622, rs1800872, and rs1800896) in the IL‐10 promoter region were successfully identified. The risk alleles, genotypes, and haplotypes were also analyzed in the CD patient group and the control group. 2 × 2 chi‐square test was used to identify whether there is a statistically significant association between CD risk and SNP polymorphisms.ResultsAccording to the chi‐square test results, only the polymorphism of rs1800872 was associated with pediatric CD. T allele in rs1800872 showed a high risk for pediatric CD (Pearson χ ² p = 0.030). TT genotype of rs1800872 was associated with a higher risk of CD in the pediatric population (OR 1.986, 95% CI 1.146–3.442, p = 0.020, TT vs. TG + GG). Finally, a risk haplotype GTT (rs3790622‐rs1800872‐rs1800896) in IL‐10 was found (OR 1.570, 95% CI 1.054–2.341, p = 0.028).ConclusionsOur data suggested that T allele, TT genotype, and haplotype GTT in rs1800872 were associated with the susceptibility to pediatric CD in China.     

Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five‐center case‐control study

BackgroundWilms tumor is the most frequent renal malignancy in children. YTHDF1 is associated with the development of several kinds of cancers, yet whether common variants of the YTHDF1 gene influence Wilms tumor risk is unknown. We present, here, a hospital‐based case‐control study specifically designed to investigate the role of YTHDF1 genetic variants on Wilms tumor.MethodsWe successfully genotyped samples of 408 Wilms tumor cases and 1198 controls which were collected from five hospitals across China. The unconditional logistic regression was adopted to analyze the contributions of YTHDF1 gene single nucleotide polymorphisms (SNPs) to the risk of Wilms tumor. The odds ratio (OR) and 95% confidence interval (CI) were generated to evaluate the conferring risk of YTHDF1 gene SNPs (rs6011668 C>T, rs6090311 A>G).ResultsNeither of the two SNPs could contribute to the risk of Wilms tumor. A negative association was also detected in the combined effects of protective genotypes on Wilms tumor risk. The stratification analysis revealed that compared with those with CC genotype, rs6011668 CT/TT genotype was associated with increased Wilms tumor risk in those ≤18 months (OR = 1.54, 95% CI = 1.02–2.30, p = 0.038), and with decreased Wilms tumor risk in those >18 months (OR = 0.70, 95% CI = 0.50–0.97, p = 0.034).ConclusionOur present work sheds some light on the potential role of YTHDF1 gene polymorphisms on Wilms tumor risk.     

A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis in Southern Han Chinese

BackgroundIdiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD‐ILD) has not been determined.MethodsA two‐stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD‐ILD cases, and 225 controls).ResultsWe identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212–4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376–4.128, p = 0.002 in stage two). However, we did not observe this association in CTD‐ILD (OR = 1.401, 95% CI = 0.790–2.485, p = 0.248).ConclusionOur findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD‐ILD.     

GSTT1, an increased risk factor for prostate cancer in patients with metabolic syndrome

BackgroundGlutathione S‐transferase (GSTs) gene polymorphism and metabolic syndrome (Mets) are generally considered to be risk factors for prostate cancer (PCa). However, this conclusion is still controversial. There is a close relationship between GSTs gene polymorphism and Mets. We suspect that the effect of GSTs gene polymorphism and Mets on PCa may be the result of their joint action. As a result, the purpose of this study was to investigate the potential effect of GSTs gene polymorphism on PCa in patients with Mets.MethodsWe collected blood samples from 128 patients with PCa and 200 controls. The GSTs gene polymorphism was detected by polymerase chain reaction‐restriction fragment length polymorphism (PCR–RFLP). Age, characteristics of Mets, frequencies of GSTs gene polymorphism, total prostate volume (TPV), Gleason score, and prostate‐specific antigen (PSA) were recorded and analyzed.ResultsThere were significant differences in BMI, TG, LDL‐C, FBG, SBP, DBP, and HDL‐C among the control group, N‐PCa group, and Mets‐PCa group (p < 0.05). GSTT1 null genotype (OR = 2.844, 95% CI: 1.791–4.517), GSTM1 null genotype (OR = 2.192, 95% CI: 1.395–3.446), and GSTP1 (A/G + G/G) genotype (OR = 2.315, 95% CI: 1.465–3.657) were associated with PCa susceptibility and malignancy. Only the GSTT1 null genotype in Mets patients was positively correlated with PCa.ConclusionsOur study suggests that GSTs gene polymorphism may be a risk factor for PCa and can predict the susceptibility and malignancy of PCa. Secondly, in Mets patients, GSTT1 null genotype significantly increased the risk of PCa. GSTM1 null genotype and the effect of GSTP1 (AG + GG) on PCa were not significantly related to Mets.     

Association between the rs3802201 polymorphism of the lncRNA MIR2052HG gene and the risk of recurrent miscarriage in a Southern Chinese population

BackgroundPlenty of studies have indicated that some genetic polymorphisms of the breast cancer which associated with its susceptibility may also be related to the susceptibility of abortion. MIR2052HG plays an important role in the onset and progression of breast cancer by maintaining the level of ERα, but to the best of our knowledge, the correlation between risk of recurrent abortion and MIR2052HG rs3802201 C>G polymorphism is still unclear. Therefore, we conducted this case‐control study to investigate whether MIR2052HG rs3802201 C>G polymorphism is associated with susceptibility of recurrent miscarriage (RM).MethodsWe recruited 392 healthy controls and 248 patients with RM to process this research, the participants were all from southern China, and genotyping was performed by TaqMan method.ResultsOur results showed that there was no evidence indicates the MIR2052HG rs3802201 C>G is related to RM (CG and CC: adjusted OR = 0.970, 95% CI = 0.694–1.355, p = 0.8577; GG and CC: adjusted OR = 0.743, 95% CI = 0.416–1.330, p = 0.3174; dominant model: adjusted OR = 0.925, 95% CI = 0.672–1.272, p = 0.6298; recessive model: adjusted OR = 0.751, 95% CI = 0.430–1.321, p = 0.3233).ConclusionWe verified that the MIR2052HG rs3802201 C>G allele might be uncorrelated to the RM risk, but these findings require further validation in multicenter studies with larger sample size and different ethnicities.     

Macrophage migration inhibitory factor gene polymorphisms (SNP ‐173 G>C and STR‐794 CATT5‐8) confer risk of plaque psoriasis: A case–control study

BackgroundMacrophage inhibitory factor (MIF) is a pro‐inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP ‐173 G> C and STR ‐794 CATT_5‐8 polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population.MethodsWe genotyped both MIF polymorphism (rs5844572 and rs755622) in 224 PP patients with a clinical and histopathological diagnosis and 232 control subjects (CS) by the PCR‐RFLP method. MIF serum levels were determined by an ELISA kit.ResultsWe found significant differences in the genotypic and allelic frequencies for the MIF ‐173 G>C polymorphism; carriers of the GC genotype (OR 1.51, 95% CI 1.026–2.228, p = 0.03) and the C allele (OR 1.34, 95% CI 1.005–1.807, p = 0.04) had higher odds to present with PP. Moreover, the 6C haplotype was associated with PP risk (OR 2.10, 95% CI 1.22–3.69, p < 0.01). Also, the ‐173 CC genotype was associated with high MIF serum levels (p < 0.05).ConclusionsThe ‐173 GC genotype and the 6C haplotype of the MIF polymorphisms are associated with susceptibility to PP in the Mexican population.     

An SNP reducing SNORD105 and PPAN expression decreases the risk of hepatocellular carcinoma in a Chinese population

BackgroundWith hepatocellular carcinoma (HCC) becoming a heavy disease burden in China, it is particular to reveal its pathological mechanism. Recent researches have indicated that small nucleolar RNAs (snoRNAs) may be involved in various cancers including HCC. Polymorphisms within snoRNAs may affect its function or expression level, and even its host gene, then produce series of effects related to itself or its host gene.MethodsThe association of the single nucleotide polymorphism (SNP) rs2305789 in SNORD105 with HCC susceptibility was evaluated in two independent case‐control sets (712 HCC and 801 controls). The contribution of rs2305789 to HCC risk was investigated using case‐control, genotype‐phenotype correlation analysis, and functional assays.ResultsThe SNP rs2305789 was significantly associated with a decreased risk of HCC in both case‐control sets (OR = 0.80, 95% CI: 0.69–0.93, p = 0.003). Compared with the AA genotype, the GG genotype was significantly correlated with lower expression of both SNORD105 and PPAN (p < 0.01). Furthermore, the overexpressed SNORD105 up‐regulated PPAN expression level (p < 0.05). Finally, the in vivo experiment showed that the overexpressed SNORD105 increased cell viability and motility in both HepG2 and Huh7 cell lines (p < 0.05).ConclusionsTo sum up, our results suggested that rs2305789 decreased the risk of HCC by reducing the expression of both SNORD105 and PPAN, which reduced HCC cell viability and motility.     

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study

BackgroundRecurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor‐related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP.MethodsA case–control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real‐time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program.ResultsHPV‐6 and HPV‐11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994–7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele.ConclusionThe G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.     

Effects of IL‐32 polymorphisms and IL‐32 levels on the susceptibility and severity of coronary artery disease

BackgroundInterleukin‐32 (IL‐32) has long been proposed as a biomarker for coronary artery disease (CAD). We aimed to evaluate the association between IL‐32 levels and coronary stenosis severity, IL‐32 polymorphisms rs28372698 and rs4786370, and CAD susceptibility.MethodsA total of 362 patients with definite or suspected CAD that underwent angiography were recruited (CAD group, n = 175; nonobstructive CAD group, n = 56; control group, n = 131). The severity of coronary stenosis was assessed using the Gensini score and the number of diseased vessels. IL‐32 levels were determined using enzyme‐linked immunosorbent assay. Gene polymorphisms were genotyped using PCR and sequencing techniques.ResultsIL‐32 levels were significantly different at different levels of coronary artery stenosis (p < 0.05), and logIL‐32 was positively correlated with the Gensini score (r = 0.357, p < 0.01). Multivariate logistic regression analysis revealed that IL‐32 was independently associated with CAD (OR = 6.526, 95% CI: 3.344–12.739, p < 0.01). The receiver operating characteristic analysis revealed the area under the curve for discriminating the CAD and Gensini score were 0.605 and 0.613, respectively. Furthermore, IL‐32 levels were significantly higher before percutaneous coronary intervention (PCI) than at 7 days post‐PCI (p = 0.012). The homozygous TT genotype and T allele of rs28372698 were found to be associated with increased risk of CAD, while TT homozygosity and the T allele of rs4786370 with reduced risk of CAD (p < 0.05). However, both SNPs had no obvious effect on IL‐32 levels or coronary stenosis severity in patients with CAD.ConclusionTo the best of our knowledge, our study is the first to show that rs28372698 and rs4786370 are associated with CAD susceptibility in Chinese Han population. We also suggest that plasma IL‐32 levels may be indicative of coronary artery stenosis and the efficacy of PCI and provide guidance for risk stratification and disease management.     

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

BackgroundDue to the loss of responsiveness to insulin, diabetes mellitus (DM) patients develop increased platelet reactivity and reduced response to antiplatelet agents. Nevertheless, the relationship between the single‐nucleotide polymorphisms (SNP) of the signal pathway gene of insulin secretion and the effect of clopidogrel is elusive.MethodsBlood samples were collected from patients administered with dual‐antiplatelet therapy (clopidogrel, 75 mg, once daily and aspirin, 100 mg, once daily) after 5 days and completed test within 4 h. The VerifyNow P2Y12 assay was used to measure the platelet functions, and the results were expressed as a P2Y12 reaction unit (PRU). Notably, the selected SNPs were analyzed to demonstrate the functionality of genetic variants.ResultsAnalysis of the study population showed that old age, lower plasma albumin (ALB) level, higher creatinine (CREA) level, higher uric acid (UA) level, lower platelet (PLT) count, and lower plateletcrit (PCT) potentially increased the risk of clopidogrel resistance. In a single‐nucleotide polymorphism rs6056209 of the PCLB1 gene, the AG genotype was a risk factor for clopidogrel resistance (p < 0.05, OR = 1.574). Similarly, the CC and AG genotype in GNAS rs7121 and CCKAR rs1800857 were protective factors (p < 0.05, OR = 0.094; p <0.05, OR = 0.491). TT was a protective factor in rs10814274 of the CREB3 gene (p < 0.05, OR = 0.444). In the RAPGEF4 gene polymorphism rs17746510, TG was the protective genotype, and the TT genotype was a risk factor for clopidogrel resistance. GCG rs5645 was confirmed; there was a relationship between genotypes containing A or G and clopidogrel resistance.ConclusionSingle‐nucleotide polymorphisms of insulin secretion signaling pathway genes trigger clopidogrel resistance.     

Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti‐tuberculosis drug‐induced hepatotoxicity: A prospective study

BackgroundThe role of collagen type XVIII alpha 1 chain (COL18A1) in anti‐tuberculosis drug‐induced hepatotoxicity (ATDH) has not been reported. This study aimed to explore the association between of COL18A1 variants and ATDH susceptibility.MethodsA total of 746 patients were enrolled in our study from December 2016 to April 2018, and all subjects in the study signed an informed consent form. The custom‐by‐design 2x48‐Plex SNPscanTM kit was used to genotype all selected 11 SNPs. Categorical variables were compared by chi‐square (χ²) or Fisher''s exact test, while continuous variables were compared by Mann‐Whitney''s U test. Plink was utilized to analyze allelic and genotypic frequencies, and genetic models. Multivariate logistic regression analyses were used to adjust potential factors. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were also calculated.ResultsAmong patients with successfully genotyping, there were 114 cases and 612 controls. The mutant A allele of rs12483377 conferred the decreased risk of ATDH (OR = 0.13, 95%CI: 0.02–0.98, P = 0.020), and this significance still existed after adjusting age and gender (P = 0.024). The mutant homozygote AA genotype of rs12483377 was associated with decreased total protein levels (P = 0.018).ConclusionOur study first revealed that the A allele of COL18A1 rs12483377 was associated with the decreased risk of ATDH in the Western Chinese Han population, providing new perspective for the molecular prediction, precise diagnosis, and individual treatment of ATDH.     

Cautions on the laboratory indicators of COVID‐19 patients on and during admission

BackgroundDifferent disease severities of COVID‐19 patients could be reflected on clinical laboratory findings.MethodsIn this single‐centered retrospective study, demographic, clinical, and laboratory indicators on and during admission were compared among 74 participants with mild, moderate, critical severe, or severe classification. Risk factors associated with disease severity were analyzed by multivariate analyses. The AUC and 95% CI of the ROC curve were calculated.ResultsThe most common manifestations of these patients were fever and cough. Critical severe or severe group owned the longest length of stay (23 (19,31), p < 0.001). After multivariate logistic regression, independent influence factors on admission for severity of disease were CK‐MB (OR 0.674; 95% CI 0.489–0.928; p = 0.016), LDH (OR 1.111 or 1.107; 95% CI 1.026–1.204 or 1.022–1.199; p = 0.009 or 0.013), normal T‐BIL (OR 4.58 × 10⁻⁸; 95% CI 3.05 × 10⁻⁹–6.88 × 10⁻⁷; p < 0.001), LYM% (OR 0.008; 95% CI 0–0.602; p = 0.029), and normal ESR (OR 0.016; 95% CI 0–0.498; p = 0.019). Factors during hospitalization were normal T‐BIL (OR 8.56 × 10⁻⁹; 95% CI 8.30 × 10⁻¹⁰–8.83 × 10⁻⁸; p < 0.001), LYM (OR 0.068; 95% CI 0.005–0.934; p = 0.044), albumin (OR 0.565; 95% CI 0.327–0.977; p = 0.041), and normal NEU% (OR 0.013; 95% CI 0.000–0.967; p = 0.048). Combined indicators of AUC were 0.860 (LYM, LDH, and normal ESR on admission, p < 0.001) and 0.750 (CK‐MB, LDH, and normal T‐BIL during hospitalization, p = 0.020) when predicting for severe or critical severe patients.ConclusionTo pay close attention to the progression of COVID‐19 and take measures promptly, we should be cautious of the laboratory indicators when patients on admission especially CK‐MB, LDH, LYM%, T‐BIL as well as ESR; and T‐BIL, LYM, albumin, NEU% with the process of disease.     

ALDH2 gene rs671 G > a polymorphism and the risk of colorectal cancer: A hospital‐based study

BackgroundThe susceptibility to some cancers is linked to genetic factors, such as aldehyde dehydrogenase 2 (ALDH2) polymorphisms. The relationship between ALDH2 rs671 and colorectal cancer (CRC) is not clear in Hakka population.MethodsBetween October 2015 and December 2020, a total of 178 CRC patients and 261 controls were recruited. ALDH2 rs671 was genotyped in these subjects, medical records (smoking history, drinking history and blood cell parameters) were collected, and the relationship between these information and CRC was analyzed.ResultsThe proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype was 48.3%, 44.4%, and 7.3% in patients; 62.1%, 34.1%, and 3.8% in controls, respectively. The difference of ALDH2 genotypes distribution between cases and controls was statistically significant (p = 0.011). The higher percentage of smokers and alcoholics, higher level of neutrophil to lymphocyte ratio (NLR), platelet count, and platelet to lymphocyte ratio (PLR), and lower level of lymphocyte count, lymphocyte to monocyte ratio (LMR), and mean hemoglobin concentration were observed in patients. Logistic regression analysis indicated that ALDH2 rs671 G/A genotype (G/A vs. G/G) (adjusted OR 1.801, 95% CI 1.160–2.794, p = 0.009) and A/A genotype (A/A vs. G/G) (adjusted OR 2.630, 95% CI 1.041–6.645, p = 0.041) in the co‐dominant model, while G/A + A/A genotypes (G/A + A/A vs. G/G) (adjusted OR 1.883, 95% CI 1.230–2.881, p = 0.004) in the dominant model were risk factors for CRC.ConclusionsIndividuals carrying ALDH2 rs671 A allele (G/A, A/A genotypes) may be at increased risk of colorectal cancer.