Association of miR-146a rs2910164 with childhood IgA nephropathy.

BACKGROUND: Micro-RNAs (miRNAs) play important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate the association between three single nucleotide polymorphisms (SNPs) (mir-146a rs2910164, let-7a-2 rs1143770, miR-196a2 rs11614913) and susceptibility to and severity of childhood immunoglobulin A (IgA) nephropathy (IgAN). METHODS: We genotyped three miRNA SNPs in two independent Han Chinese populations composed of 158 patients and 265 controls (discovery set), and 246 patients and 446 controls (validation set), respectively. RESULTS: We found that rs2910164 was significantly associated with IgAN in the discovery but not the validation set. Combined analysis revealed that rs2910164 CC and CG genotypes were associated with increased risk of IgAN compared with the GG genotype [adjusted odds ratios (OR) = 1.684, 95 % confidence interval (CI)1.190-2.384, P = 0.003; adjusted OR = 1.472, 95 % CI 1.079-2.007, P = 0.015, respectively). We also found that the frequency of the rs2910164 CC genotype was significantly higher in patients with Haas grade III-V than in those with Haas grade I-II for all study populations (P < 0.05). The expression of miR-146a in normal renal tissues with CC genotype was lower than in those with a G allele (P = 0.038). CONCLUSIONS: These results indicated that rs2910164 may affect the susceptibility and severity of pediatric IgAN. Further studies are needed to validate these findings.

A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma.

BACKGROUND: It is of great concern to identify prognostic signatures for the prediction and prediction of esophageal squamous cell carcinoma (ESCC), which is the lethal pathological type of malignancy. METHOD: Bulk RNA sequencing and scRNA-seq data were retrieved from GSE53624, GSE53622, and GSE188900. Disulfidptosis-related differentially expressed genes (DEGs) were identified between disulfidptosis-high score and disulfidptosis-low score groups. Functional annotation of DEGs were analyzed by Gene Ontology (GO). Consistent clustering and co-expression modules were analyzed, and then constructed a risk score model via multivariate Cox regression analysis. Immune infiltration and immunotherapy response analyses were conducted based on risk score. qRT-PCR, colony formation assay, and flow cytometry analysis were conducted in KYSE-150 and TE-1 cell lines. RESULTS: Seven genes (CD96, CXCL13, IL2RG, LY96, TPK1, ACAP1, and SOX17) were selected as marker genes. CD96 and SOX17 are independent prognostic signatures for ESCC patients, with a significant correlation with infiltrated immune cells. ESCC patients had worse response to nivolumab in the high-risk group. Through cellular experiments, we found that CD96 expression was associated with apoptosis and cell cycle ESCC cells. CONCLUSION: In a word, the risk score based on disulfidptosis is associated with prognosis and the immune microenvironment, which may direct immunotherapy of ESCC. The key gene of risk score, namely CD96, plays a role in proliferation and apoptosis in ESCC. We offer an insight into the exploration of the genomic etiology of ESCC for its clinical management.

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Background: Inflammation is not only involved in the development and progression of cancer but also affects the response to therapy. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in inflammation genes with the prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Methods: Forty-seven SNPs were genotyped in 318 advanced NSCLC patients receiving EGFR-TKIs. Of 318 patients, 182 (57.2%) patients died during follow-up period. We assessed the association of SNPs with the progression-free survival (PFS) and overall survival (OS) as well as calculated the weighted genetic risk score (GRS). We also explored the expression levels and prognostic values of inflammation genes in lung adenocarcinoma (LUAD) in Gene Expression Profiling Interactive Analysis (GEPIA) and using UCSC Xena, respectively. The relationship between the expression levels of IL15, IL17RA, AGER, MIF, and TNFRSF1A and EGFR mutation status was analyzed using UCSC Xena. Results: In single variant analyses, 3 SNPs (rs10519613, rs4819554, and rs4149570) were significantly associated with worse PFS. Five SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were significantly with worse OS. In addition, high and intermediate GRSs (based on rs10519613, rs4819554, and rs4149570) were associated with worse PFS than those with low GRS. For OS, patients with high GRSs (based on rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) had shorter survival time than those with low GRS. Furthermore, IL15, IL17RA, AGER, MIF, and TNFRSF1A were dysregulated in LUAD. There was difference in the expression level of TNFRSF1A between EGFR wildtype and EGFR-mutant LUAD. Both low AGER expression and high TNFRSF1A expression were significantly associated with worse PFS in LUAD. In addition, low IL17RA and AGER expression, high MIF and TNFRSF1A expression were significantly associated with worse OS in LUAD. Conclusion: SNPs in inflammation genes could serve as prognostic biomarkers for NSCLC patients treated with EGFR-TKIs.

Haplotype-based association of four lymphotoxin-alpha gene polymorphisms with the risk of coronary artery disease in Han Chinese.

Lymphotoxin-alpha (LTA), a pro-inflammatory cytokine, has been implicated in the pathogenesis of coronary atherosclerosis. Meanwhile, association of some single nucleotide polymorphisms (SNPs) of LTA gene with coronary artery disease (CAD) has been evaluated; however, the results are irreproducible. We therefore investigated the relationship between four SNPs of LTA gene and CAD in Han Chinese: G+10A (rs1800683, 5'-untranslated region), A+80C (rs2239704, 5'-untranslated region), T+496C (Cys13Arg, rs2229094, exon 2), and C+804A (Thr26Asn, rs1041981, exon 3). Genotyping was performed in 438 CAD patients and 330 healthy controls. Single-locus analysis showed that the genotype and allele frequencies of G+10A polymorphism exhibited marginal differences between CAD patients and controls, although no statistical significance was observed after the Bonferroni correction. Logistic regression analysis revealed that GG genotype of G+10A polymorphism was significantly associated with the risk of CAD under the dominant mode, whereas no significant association was detected between A+80C polymorphism and CAD. In contrast, individuals carrying TT or TC genotype of T+496C polymorphism showed a decreased CAD risk relative to those with CC genotype under the recessive mode. Likewise, CC genotype of C+804A polymorphism was associated with a protective effect on CAD under the dominant mode. Further, in haplotype analysis, the haplotype G-C-T-C (in order of rs1800683, rs2239704, rs2229094 and rs1041981) was significantly associated with a decreased risk of CAD after assigning the most common haplotype A-C-T-A as a reference. In conclusion, we show a protective effect of the haplotype G-C-T-C on the occurrence of CAD, suggesting the involvement of LTA in CAD pathogenesis.

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.

Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.

[A new SNP microarray technology based on single base extension].

Investigation of DNA-protein interactions is fundamental to understand the mechanism underlying a variety of life processes. In this article, various types of biochemical methods in DNA-protein interaction study in vivo and in vitro at the level of DNA, protein, and the complex, respectively were briefly reviewed. Traditional assays including Nitrocellulose filter-binding assay, Footprinting, EMSA, and Southwestern blotting were summarized. In addition, chromatin immunopre-cipitation techniques including nChIP, xChIP, and ChIP-on-chip, which were widely used in epigenetics, were particularly introduced.

The Relationship Between ZEB1-AS1 Expression and the Prognosis of Patients With Advanced Gastric Cancer Receiving Chemotherapy.

Long noncoding RNA ZEB1 antisense RNA 1 plays a vital role in tumorigenesis and metastasis. However, the role of ZEB1 antisense RNA 1 in gastric cancer remains unclear. This study aimed to investigate the expression level of ZEB1 antisense RNA 1 in gastric cancer tissues and evaluate its association with clinicopathological features and prognosis of patients with advanced gastric cancer receiving chemotherapy. The expression levels of ZEB1 antisense RNA 1 were examined in 224 pairs of gastric cancer and adjacent noncancerous tissues by quantitative real-time polymerase chain reaction. The associations between ZEB1 antisense RNA 1 expression and clinicopathological features or survival of patients with advanced gastric cancer were assessed. The results showed that the expression levels of ZEB1 antisense RNA 1 in gastric cancer tissues were significantly higher than those in the paracancerous tissues ( P < .001). Moreover, the high ZEB1 antisense RNA 1 expression was associated with tumor, nodes, and metastases stage IV ( P = .018) and loss of E-cadherin expression ( P = .033). Multivariate Cox hazards regression analysis revealed that high ZEB1 antisense RNA 1 expression was an independent risk factor for predicting poor prognosis in patients with advanced gastric cancer (hazard ratio = 1.530, 95% confidence interval, 1.052-2.224, P = .026). In conclusion, the present findings suggest that ZEB1 antisense RNA 1 is an independent prognostic factor for patients with advanced gastric cancer receiving chemotherapy.

MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC. METHODS: Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells. RESULTS: The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects. CONCLUSION: miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.

Increased expression of plakophilin 3 is associated with poor prognosis in ovarian cancer.

Considering the essential role of plakophilin 3 (PKP3) in the maintenance cell-cell adhesion, dysregulation of PKP3 is involved in human diseases. This study aimed to explore the clinical significance of PKP3 in ovarian cancer. Immunohistochemistry was performed to examine the PKP3 expression in 157 cancer specimens from primary ovarian cancer patients. PKP3 was expressed in both the cytoplasm and nucleus. Eighty-one (51.6%) out of 157 ovarian cancer tissues showed PKP3 expression, while absent expression was observed in normal ovarian tissues. High PKP3 expression was associated with lymph node metastasis (LNM, P = .004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = .013). Patients with high PKP3 expression had shorter overall survival (OS) than those with low PKP3 expression (60.2 months vs 74.2 months, P = .021). However, no association between PKP3 expression and progression-free survival (PFS) was observed (P = .790). Cox regression analysis indicated that PKP3 expression was an independently predictive factor for the OS of patient with ovarian cancer (adjusted HR = 1.601, 95%CI: 1.014-2.528, P = .043), especially those with FIGO stages III and IV disease (adjusted HR = 1.607, 95%CI: 1.006-2.567, P = .047). The gene expression profiling interactive analysis (GEPIA) databases also showed that PKP3 was upregulated in ovarian cancer (P < .001) and patients with high PKP3 expression had shorter OS (P = .004). In conclusion, our findings suggest that PKP3 is upregulated in ovarian cancer and is likely involved in the progression of ovarian cancer. PKP3 might therefore serve as a prognostic biomarker for patients with ovarian cancer.

Detection of the clarithromycin resistance of Helicobacter pylori in gastric mucosa by the amplification refractory mutation system combined with quantitative real-time PCR.

The goal of this study was to evaluate the feasibility of detecting Helicobacter pylori clarithromycin resistance in gastric mucosa using the amplification refractory mutation system combined with quantitative real-time PCR (ARMS-PCR). Gastric mucosal specimens (150) were collected from patients who were unsuccessfully treated for H. pylori eradication. Each specimen was divided into 2 samples. One sample was used to extract genomic DNA and detect any gene mutations of H. pylori produced by ARMS- PCR. Sequencing was used to assess the accuracy of this method. The other sample was used to culture H. pylori. The E-test minimum inhibitory concentration (MIC) was used to assess clarithromycin resistance. The results were compared with a paired chi-square test to validate the coincidence rate among the 3 methods. The coincidence rate between the sequencing and ARMS-PCR results was 98.7%, thus verifying the accuracy of ARMS-PCR. E-tests detected 144 clarithromycin resistance cases, including 45 sensitivity cases; the resistance rate was 70%. The coincidence rate between the results of the E-test and ARMS-PCR was 97.1%, and no significant difference between the 2 methods was observed. ARMS-PCR is a simple and fast method that has high sensitivity and specificity and can be used to detect the clarithromycin resistance of H. pylori in gastric mucosa. ARMS-PCR is expected to be used to study drug resistance mechanisms and use in assays of individual therapies for H. pylori eradication.

Mediating Effect of Diabetes Mellitus on the Association Between Chromosome 9p21.3 Locus and Myocardial Infarction Risk: A Case-Control Study in Shanghai, China.

Background: Previous genome-wide association studies revealed that the chromosome 9p21.3 locus is associated with an increased risk of myocardial infarction (MI) and diabetes mellitus (DM). However, it is unclear whether the 9p21.3-MI association is direct or mediated by pathways related to DM. Study Design: We applied mediation analysis to examine the potential mediating effect of DM on the association between the 9p21.3 genetic risk score (GRS; ranged from 0 to 8) and MI in a case-control study of 865 MI patients and 927 controls without coronary artery disease (CAD). The GRS combining 4 lead 9p21.3 single nucleotide polymorphisms (rs1333040, rs4987574, rs2383207, and rs1333049) was constructed. Results: Each 1 unit increase in weighted 9p21.3 GRS was associated with a 9% increased DM risk (95% confidence interval (CI) 1.00, 1.19) in the control group and a 14% increased MI risk (95% CI 1.09, 1.20). Mediation analyses yielded a direct-effect odds ratio (OR) of 1.06 (95% CI 1.04, 1.08) and an indirect-effect OR of 1.00 (95% CI 0.99, 1.01) for weighted GRS. DM mediated 4.40% (95% CI 3.42, 6.52) of the total association between the weighted GRS and MI risk. Individuals with the highest quartile of 9p21.3 GRS and DM had a 6-fold higher MI risk than those with the lowest quartile of 9p21.3 GRS and non-DM (OR 6.03, 95% CI 3.48, 10.5). Conclusion: DM is a weak mediator that explains a small fraction of the 9p21. 3-MI association in Chinese adults. Nevertheless, there is a strong synergistic effect between DM and the 9p21.3 GRS on MI risk.

Clinical significance of ubiquilin 1 in gastric cancer.

Ubiquilin 1 (UBQLN1) plays an essential role in the regulation of protein degradations which is involved in the pathophysiology of neurodegenerative diseases and cancer. This study aimed to investigate the expression level of UBQLN1 in gastric cancer and evaluated the relationship between its expression and clinicopathological characteristics, as well as prognostic of patients with gastric cancer. Immunohistochemistry (IHC) was used to detect the expression levels of UBQLN1 in 179 pairs of gastric cancer and adjacent normal tissues. The UBQLN1 was significantly upregulated in gastric cancer tissue. High UBQLN1 expression was associated with high histological grade, invasion, lymph node metastasis, and tumor node metastasis (TNM) stage III (P < .001). Multivariate Cox analysis showed that larger tumor size (HR = 3.125, 95%CI: 2.031-4.808, P < .001), histological grade 3 (HR = 15.313, 95%,CI: 8.075-29.041, P < .001), pT3 + pT4 (HR = 3.224, 95%CI: 1.389-7.483, P = .006), LNM (HR = 4.467, 95%CI: 2.404-8.302, P < .001), TNM stage III (HR = 2.152, 95%CI: 1.289-3.594, P = .003), and high UBQLN1 expression (HR = 2.547, 95%CI: 1.511-4.292, P < .001) were significantly associated with worse prognosis of patients with gastric cancer. In conclusion, high UBQLN1 expression was an independent worse prognostic factor for patients with gastric cancer.

Retinoblastoma Binding Protein 5 Correlates with the Progression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy tumors with insidious onset, rapid development and metastasis, and poor prognosis. Therefore, it is necessary to understand molecular mechanisms of HCC and identify clinically useful biomarkers for it. This study aimed to investigate the role of retinoblastoma binding protein 5 (RBBP5) in HCC. The expression level of RBBP5 was examined by immunohistochemistry and western blot. The effect of RBBP5 on cell cycle, proliferation, apoptosis, and drug sensitivity was analyzed. RBBP5 was significantly upregulated in HCC tissues and cells. High RBBP5 expression was significantly associated with elevated level of AFP, advanced TNM stage, high Ki-67 expression, larger tumor size, and poor prognosis. Knockdown of RBBP5 significantly inhibited proliferation of HCC cells through cell cycle arrest. In addition, inhibition of RBBP5 increased the sensitivity of HCC cells to doxorubicin. In conclusion, our findings suggest that RBBP5 plays an important role in the progression of HCC and may serve as a novel biomarker and potential therapeutic target for HCC.

Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood pressure response to antihypertensive treatment.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population. METHODS: Fifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment. RESULTS: The patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P=0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P=0.030; diastolic BP: P=0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P=0.007). CONCLUSIONS: AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

[Association of thiazide-sensitive Na+-Cl* cotransporter gene polymorphisms with the risk of essential hypertension].

OBJECTIVE: To investigate the association of thiazide-sensitive Na+ -Cl* cotransporter (TSC) gene 1784C/T and 2736G/A polymorphisms with the risk of essential hypertension (EH) in a Han nationality population. METHODS: A community-based, case-control study including 190 EH patients and 94 sex- and age-matched controls was conducted. Genotypes of TSC gene 1784C/T and 2736G/A polymorphisms were analyzed by gene chip technology. RESULTS: The genotype (1784C/T CC, CT, TT:87, 88, 15 vs 36, 52, 6û2736G/A GG, AG, AA:167, 22, 1 vs 83, 10, 1) and alleles frequency (1784C/T C, T:68.9%, 31.1% vs 66.0%, 34.0%; 2736G/A G,A:93.7%, 6.3% vs 93.6%, 6.4%) distribution of 1784C/T and 2736G/A showed no significant difference between the EH group and the control group (P >0.05). Moreover, no significant difference was observed in the frequencies distribution of four haplotypes (P > 0.05); Logistic regression analysis of haplotypes showed that the risk of EH had no significant difference in the population with different haplotypes (P > 0.05). CONCLUSION: The 1784C/T and 2736G/A polymorphisms of TSC gene may not play an important role in the etiology of EH in a Han nationality population. The studies in the future are warranted to validate our findings.

Intravascular NK/T-cell lymphoma in the testis: a novel case report and review of the literature.

Intravascular NK/T-cell lymphoma (IVNKTL) is an extremely rare type of lymphoma that frequently affects the skin. To date, only 14 cases of IVNKTL have been described. To the best of our knowledge, this is the first case report of IVNKTL in the testis.

Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is an early and key process in the metastatic cascade during the progression of colorectal cancer (CRC). The aim of the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs) of CRC and assess the effect of differentially expressed miRNAs on the prognosis of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in 3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was further validated in 90 pairs of CRC and corresponding paracarcinoma tissues using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p and miR-3678-3p) were identified to be differentially expressed between different EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR-10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly increased compared with levels in corresponding paracarcinoma tissues. Survival analyses revealed that down-regulation of miR-193a-3p was associated with worse prognosis of patients with CRC, particularly in female and older patients. The results of the present study indicate that miR-193a-3p may be an EMT-related biomarker and serve as a novel prognostic factor for CRC.

Conditional Inference Tree for Multiple Gene-Environment Interactions on Myocardial Infarction.

BACKGROUND AND AIMS: Identifying gene-environment interaction in the context of multiple environmental factors has been a challenging task. We aimed to use conditional inference tree (CTREE) to strata myocardial infarction (MI) risk synthesizing information from both genetic and environmental factors. METHODS: We conducted a case-control study including 1440 Chinese men (730 MI patients and 710 controls). We first calculated a weighted genetic risk score (GRS) by combining 25 single nucleotide polymorphisms (SNPs) that had been identified to be associated with coronary artery diseases in previous genome wide association studies. We then developed a CTREE model to interpret the gene-environment interaction network in predicting MI. RESULTS: We detected high-order interactions between dyslipidemia, GRS, smoking status, age and diabetes. Of all the variables examined, high density lipoprotein cholesterol (HDL-C) of 1.25 mmlo/L was identified as the key discriminator. The subsequent splits of MI were low density lipoprotein cholesterol (LDL-C) of 4.01 mmol/L and GRS of 20.9. We found that individuals with HDL-C ≤1.25 mmol/L, GRS >20.9 and lipoprotein (a) > 0.09 g/L had a higher risk of MI than those who at the lowest risk group (OR: 5.89, 95% CI: 3.99-8.69). This magnitude of MI risk was similar to the combination of HDL-C ≤1.25 mmol/L, GRS ≤20.9, smoking and lipoprotein (a) > 0.15 g/L (OR: 5.49, 95% CI: 3.51-8.58). CONCLUSIONS: The multiple interactions between genetic and environmental factors can be visually present via the CTREE approach. The tree diagram also simplifies the decision making procedure by answering a sequence of questions along the branches.