Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults

Candidate gene studies have analyzed the effect of specific vitamin D pathway genes on vitamin D availability; however, it is not clear whether genetic variants also affect overall bone metabolism. This study evaluated the association between genetic polymorphisms in GC, CYP2R1 and CYP24A1 and serum levels of total 25(OH)D, iPTH and other mineral metabolism biomarkers (albumin, total calcium and phosphorus) in a sample of 273 older Spanish adults. We observed a significant difference between CYP2R1 rs10741657 codominant model and total 25(OH)D levels after adjusting them by gender (p = 0.024). In addition, the two SNPs in the GC gene (rs4588 and rs2282679) were identified significantly associated with iPTH and creatinine serum levels. In the case of phosphorus, we observed an association with GC SNPs in dominant model. We found a relationship between haplotype 2 and 25(OH)D levels, haplotype 4 and iPTH serum levels and haplotype 7 and phosphorus levels. In conclusion, genetic variants in CYP2R1 and GC could be predictive of 25(OH)D and iPTH serum levels, respectively, in older Caucasian adults. The current study confirmed the role of iPTH as one of the most sensitive biomarkers of vitamin D activity in vivo.

Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease

Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.

Associations of FKBP5 polymorphisms and methylation and parenting style with depressive symptoms among Chinese adolescents

Background Genetic factors may interplay with environmental stressors to contribute to risks of depressive symptoms. This study aimed to investigate the association of FKBP5 polymorphisms and DNA methylation with depressive symptoms among Chinese adolescents, considering the role of parenting style. Methods This study used a nested case-control study design based on a cohort study, and the case (n = 120) and control groups (n = 118) were matched with age. Depressive symptoms, parenting style, and other demographics were measured. Fourteen potential polymorphisms and one promoter region in the FKBP5 gene were selected for genotyping and methylation analysis. Results In the adjusted models, a significant association between FKBP5 rs7757037 and depressive symptoms was found in the codominant model (AG vs. GG; adjusted odds ratio [AOR] = 2.56, 95% CI = 1.13–5.78) and dominant model (AA+AG vs. GG; AOR = 2.38, 95% CI = 1.11–5.120); rs2817032 and rs2817035 polymorphisms were associated with depressive symptoms in the codominant model and dominant model. Significant interactions between rs7757037 and the father’s parenting style were found in the codominant model (P = 0.043) and dominant model (P = 0.043), but the gene-environment interactions were not significant after correcting for multiple testing. Moreover, the significant main effects of FKBP5 methylation status on depressive symptoms were not observed, and there was no significant interaction between FKBP5 methylation status and parenting style on depressive symptoms. Conclusions Further studies are required to confirm the effect of FKBP5 polymorphisms and methylation as well as their interactions with parenting styles in larger samples.

Associations of FKBP5 Polymorphisms and Methylation and Parenting Style With Depressive Symptoms Among Chinese Adolescents

Background Genetic factors may interplay with environmental stressors to contribute to risks of depressive symptoms. This study aimed to investigate the association of FKBP5 polymorphisms and DNA methylation with depressive symptoms among Chinese adolescents, considering the role of parenting style. Methods This study used a nested case-control study design based on a cohort study, and the case (n = 120) and control groups (n = 118) were matched with age. Depressive symptoms, parenting style, and other demographics were measured. Fourteen potential polymorphisms and one promoter region in the FKBP5 gene were selected for genotyping and methylation analysis. Results In the adjusted models, a significant association between FKBP5 rs7757037 and depressive symptoms was found in the codominant model (AG vs. GG; adjusted odds ratio [AOR] = 2.37, 95% CI = 1.07–5.28) and dominant model (AA + AG vs. GG; AOR = 2.22, 95% CI = 1.05–4.69); rs2817032 polymorphism was associated with depressive symptoms in the codominant model and dominant model. Significant interactions between rs7757037 and the father’s parenting style were found in the codominant model (P = 0.037) and dominant model (P = 0.038), but the gene-environment interactions were not significant after correcting for multiple testing. The main and interactive effects of FKBP5 methylation status on depressive symptoms were not observed, and no significant mediations were found in the association between FKBP5 polymorphisms and depressive symptoms through the methylation mechanism. Conclusions Further studies are required to confirm the effect of FKBP5 polymorphisms and methylation as well as their interactions with parenting styles in larger samples.

Impact of COL6A4P2 gene polymorphisms on the risk of lung cancer: A case-control study

Lung cancer (LC) is a malignant tumor that poses the greatest threat to human health and life. Most studies suggested that the occurrence of LC is associated with environmental and genetic factors. We aimed to explore the association between COL6A4P2 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese Southern Han population. Based on the ‘case-control’ experimental design (510 cases and 495 controls), we conducted an association study between five candidate COL6A4P2 SNPs and the corresponding LC risk. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression to analyze the LC susceptibility under different genetic models. The results showed that COL6A4P2 rs34445363 was significantly associated with LC risk under alleles model (OR = 1.26, 95%CI: 1.01–1.58, p = 0.038). In addition, rs34445363 was also significantly associated with LC risk under the log-additive model (OR = 1.26, 95%CI: 1.01–1.58, p = 0.041). The results of subgroup analysis showed that rs34445363 (OR = 1.42, 95%CI: 1.03–1.95, p = 0.033) and rs61733464 (OR = 0.72, 95%CI: 0.52–0.99, p = 0.048) were both significantly associated with LC risk in the log-additive model among participants who were ≤ 61 years old. We also found that the variation of rs34445363 (GA vs. GG, OR = 1.73, 95%CI: 1.04–2.86, p = 0.034) and rs77941834 (TA vs. TT, OR = 1.88, 95%CI: 1.06–3.34, p = 0.032) were associated with LC risk in the codominant model among female participants. Our study is the first to find that COL6A4P2 gene polymorphism is associated with LC risk in the Chinese Han population. Our study provides a basic reference for individualized LC prevention.

Variants Around miR-451 Can Affect the Risk of Large-artery Atherosclerosis Stroke in Chinese

Background: Ischemic stroke has high incidence rate, mortality rate and disability rate. Genetic factors have a significant impact on stroke risk. MicroRNAs are a class of small non-coding RNA. Intergenic variants can affect the regulation of microRNAs and modulate large-artery atherosclerosis stroke susceptibility. The low expression of miR-451 aggravated ischemic injury significantly.Methods: Functional intergenic variants near hsa-mir-451 were identified by bioinformatics analysis. We conducted a case-control study to explore the associations of selected variants with large-artery atherosclerosis stroke risk in Chinese.Results: The rs901975 (G>A) near hsa-mir-451 was identified as a functional SNP for stroke susceptibility. The protective effect of A allele was significant in codominant model (OR = 0.62, 95% CI = 0.44-0.89, P = 0.005), recessive model (OR = 0.65, 95% CI = 0.47-0.89, P = 0.006) and log-additive model (OR = 0.82, 95% CI = 0.71-0.96, P = 0.012). We also found the significant effect in participants over 65 years old, male, hypertensive and diabetic people. Moreover, hypertensive people genotyped as GG+GA had 2.84 - fold increased risk compared with those genotyped as AA without hypertension (P interaction = 0.036). In the MEGASTROKE Consortium, rs901975 A allele also had protective effect on LAA stroke in Europeans (OR = 0.937, 95% CI: 0.882-0.996, P = 0.036). Combined analysis of our study and MEGASTROKE showed consistent trend (OR = 0.920, 95% CI: 0.869-0.973, P = 0.004).Conclusions: Our study suggested that rs901975 near hsa-mir-451 might affect large-artery atherosclerosis stroke susceptibility in Chinese population.

Association of ST6GAL1 and CYP19A1 polymorphisms in the 3′-UTR with astrocytoma risk and prognosis in a Chinese Han population

Background Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and prognosis of astrocytoma. Methods A total of 365 astrocytoma patients and 379 healthy controls were genotyped using the Agena MassARRAY system. The correlation between ST6GAL1 and CYP19A1 variants and astrocytoma risk was calculated using logistic regression. The survival rate of patients with astrocytoma was analyzed to evaluate prognosis. Results We found that the ST6GAL1-rs2239611 significantly decreased the risk of astrocytoma in the codominant model (p = 0.044) and dominant model (p = 0.049). In stratified analyses, CYP19A1-rs2255192 might be associated with a higher risk of astrocytoma among the low-grade subgroup under recessive (p = 0.034) and additive (p = 0.030) models. However, CYP19A1-rs4646 had a risk-decreasing effect on the high-grade subgroup in the codominant model (p = 0.044). The results of Cox regression analysis showed that the CYP19A1-rs2239611 and -rs1042757 polymorphisms were significantly correlated with the prognosis of astrocytoma. Conclusion Our results suggest that ST6GAL1 and CYP19A1 genes may be a potential biomarker of genetic susceptibility and prognosis to astrocytoma in the Chinese Han population.

Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population

Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary.Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL.Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne® thermal cycler (Applied Biosystems, United States).Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880–7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05).Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.

Impact of Proliferator-Activated Receptor γ Gene Polymorphisms on Risk of Schizophrenia: A Case-Control Study and Computational Analyses

Objective: Schizophrenia (SCZ) is a common psychiatric disorder characterized by a complex mode of inheritance. Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. This preliminary study was aimed to investigate the relationship of two polymorphisms in the PPARG gene, rs1801282 C/G, and rs3856806 C/T, to the risk of SCZ in the southeast Iranian population. Method: A total of 300 participants (150 patients with SCZ and 150 healthy controls) were enrolled. Genotyping was done using the amplification refractory mutation system polymerase chain reaction (ARMS–PCR) technique. Computational analyses were carried out to predict the potential effects of the studied polymorphisms. Results: A significant link was found between genotypes of rs1801282 and SCZ susceptibility. The G allele of rs1801282 in CG and GG form of the codominant model increased the risk of SCZ by 2.49 and 2.64 folds, respectively. With regards to rs3856806, enhanced risk of SCZ was also observed under different inheritance models except for the overdominant model. Also, the T allele of rs3856806 enhanced the risk of SCZ by 3.19 fold. Computational analyses predicted that rs1801282 polymorphism might alter the secondary structure of PPARG-mRNA and protein function. At the same time, the other variant created the binding sites for some enhancer and silencer motifs. Conclusion: Our findings showed that PPARG rs1821282 and rs3856806 polymorphisms associate with SCZ susceptibility. Replication studies in different ethnicities with a larger population are needed to validate our findings.

Association of TLR-2 Gene Polymorphisms with the Risk of Periodontitis: A Meta-Analysis

Background. Periodontitis is a kind of chronic infectious disease, affecting the health of billions of people. In recent years, a number of studies have shown that multiple immune gene polymorphisms are associated with the susceptibility to periodontitis, among which TLR-2 plays a critical role in periodontitis. But most of the studies reported TLR-2 gene polymorphism and susceptibility to periodontitis are not consistent. Therefore, we included all eligible studies in our study for further meta-analysis. Methods. We used electronic databases, including CNKI, PubMed, EMBASE, and Web of Science databases, and relevant research published through June, 2020. Selecting studies involved case-control trials. For all eligibility studies, odds ratios (ORs) and 95% confidence intervals (95% CI) are provided or can be calculated from the study data. The size of the combined effect was calculated using STATA 15.0. Results. Our meta-analysis included 14 articles representing 18 case-control studies with a total of 3873 cases and 3438 control subjects. Significant association was found between periodontitis and TLR-2 rs1898830 polymorphism under the allelic model (A allele vs. G allele: p=0.014, OR=1.208, 95% CI: 1.039-1.406), recessive model (GG vs. GA+AA: p=0.028, OR=0.755, 95% CI: 0.588-0.970), and codominant model (GG VS. AA: p=0.014, OR=0.681, 95% CI: 0.501-0.925). In subgroup analysis, TLR-2 rs5743708 polymorphism was associated with periodontitis risk in Asians under an allelic model (G allele vs. A allele: p=0.017, OR=12.064, 95% CI: 1.570-92.688), dominant model (GA+AA vs.GG: p=0.016, OR=0.08, 95% CI: 0.010-0.620), and codominant model (GA VS. GG: p=0.016, OR=1.026, 95% CI: 0.821-1.282). Conclusion. The TLR-2 rs1898830, rs5743708 polymorphism may be associated with susceptibility to periodontitis. In the future, genome-wide approaches and large-scale, multiethnic case-control trials are still needed.