Genetic testing and molecular biomarkers最新文献

Introduction: Obstructive sleep apnea (OSA) syndrome is a widespread multifactorial disorder that raises the risk of cardiovascular disease, diabetes, and Alzheimer's disease. This study aimed to investigate the association between the risk of OSA and two C-reactive protein (CRP) gene variants, rs1130864 and rs2794521. Materials and methods: In this study, 100 patients and 100 controls participated. Among 500 patients with OSA attending the sleep disorder center, 100 were randomly selected from those with apnea/hypopnea symptoms and daytime sleepiness. Polymerase chain reaction and restriction fragment length polymorphism of the CRP gene polymorphisms were used in this investigation. Results: The frequency of the mutant C allele was higher in the patient group than in the control group for the rs2794521 CRP gene variant (p ≤ 0.001), and the C allele elevated the risk of OSA by 2.584 times (odds ratios = 2.584, 95% confidence interval). The frequency of the mutant T allele was higher in the patient group than in the control group for the rs1130864 CRP gene variant, while the frequency of the C allele was higher in the control group, and this difference was statistically significant (p ≤ 0.001). Conclusions: Our findings indicated that rs1130864 and rs2794521 of the CRP gene are associated with increased risk for OSA. Extensive research is required to determine the role of distinct CRP gene variants in OSA.

Background: Idiopathic clubfoot (IC) can be corrected initially using the Ponseti method, but still there is a high recurrence rate. The etiology of IC may include many undetermined genetic and environmental factors. Single nucleotide polymorphism of rs274503 in ZBED5/GALNT18 has been found to be associated with IC in Caucasian children. Therefore, we decided to investigate the association between this polymorphism and the risk of IC in the Chinese population. Methods: We conducted an 11-center case-control study of 516 patients with IC and 661 IC-free children. The rs274503 (A>G) polymorphism was genotyped using TaqMan. Odds ratios (ORs) and adjusted ORs, as well as 95% confidence intervals (CIs) and adjusted 95% CIs, were calculated to explore the association between rs274503 polymorphism and IC risk. Results: G of rs274503 was found to be associated with increased IC risk (AG vs. AA: adjusted OR = 1.40, 95% CI = 1.03-1.92, p = 0.0327; and GG/AG vs. AA: adjusted OR = 1.38, 95% CI = 1.02-1.87, p = 0.0357) after adjusting for age and sex. Furthermore, the risk effect of rs274503 GG/AG with IC was observed in patients with bilateral feet (adjusted OR = 1.68, 95% CI = 1.12-2.54, p = 0.0133), while AA in nonrelapsed groups (OR = 0.70, 95% CI = 0.53-0.92, p = 0.0095) in the stratified analysis. However, the association was not significant in the recessive model of G (GG vs. AA/AG: adjusted OR = 1.06, 95% CI = 0.44-2.58, p = 0.8906). Conclusions: The rs274503 polymorphism is associated with the risk of clubfoot occurrence. G of rs274503 appeared to be a risk factor of IC as it may increase the bilateral case rate. However, further studies are required to confirm these findings.

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease. The renin-angiotensin system (RAS) plays an important role in the development of IgAN. Polymorphisms in genetic loci coding for the RAS may be associated with IgAN progression. Methods: We analyzed the M235T, A1166C, and A1675G polymorphisms in 297 IgAN patients, and analyzed their associations with clinical manifestations, pathological damage, effects of RAS-inhibitor treatment, and IgAN patient prognosis. Results: In patients with the A1675G polymorphism, creatinine levels were significantly lower in those with the AG genotype than in those with the AA genotype (p = 0.023). However, this difference was not significant when creatinine levels were analyzed according to sex. Patients with endocapillary proliferation according to the Oxford Classification of IgAN were less likely to have the AG genotype than the AA genotype (p = 0.025). In IgAN patients treated with angiotensin-II-receptor blockers, 24-h urine protein levels were lower in patients with the AC genotype of A1166C than in those with the AA genotype at baseline and follow-up (Base p = 0.013, 1 month p = 0.0035, 3 months p = 0.009). Cox regression analysis implied that the three gene polymorphisms were not independent risk factors for the prognosis of IgAN. Conclusion: The AG genotype of A1675G may confer protection against the development of IgAN, with a stronger protective effect observed in females. M235T, A1166C, and A1675G do not appear to be independent risk factors for IgAN.

Background: COVID-19 is one of the worst pandemics worldwide, and its diagnosis and treatment are of great importance. Recent evidence has shown that circular RNA (circRNA deregulation is involved in different infectious diseases. In the present study, we tried to investigate the expression of cirRNAs RasGEF1B (hsa_circ_0127052), HIPK3 (hsa_circ_100783), and GATAD2A (hsa_circ_0050236) in COVID-19 patients. Methods: Using quantitative real-time polymerase chain reaction, the expression profiles of candidate circRNAs were detected in 57 COVID-19 patients and 51 healthy controls. As part of the process of identifying a candidate circRNA that is sensitive and specific, receiver operating characteristic (ROC) curves were also utilized. Results: Our results showed higher expression levels of circRasGEF1B and circHIPK3 in COVID-19 patients, however, circGATAD2A showed no statistical difference between patients and controls. ROC curves showed that circRasGEF1B (hsa_circ_0127052), and HIPK3 (hsa_circ_100783) had favorable specificity and sensitivity, whereas GATAD2A (hsa_circ_0050236) did not. Conclusion: In summary, our study highlights the potential of CircRasGEF1B (hsa_circ_0127052) and HIPK3 (hsa_circ_100783) as biomarkers for COVID-19 diagnosis due to their high expression levels and demonstrated diagnostic accuracy. These findings suggest that circRNAs could play a crucial role in the development of diagnostic tools for COVID-19, providing a new avenue for early detection and management of the disease.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

Objective: To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. Methods: WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups. Results: The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes (FBN1, SMAD3, TGFBR2, TGFB2, and MYLK) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for ≤35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences (p = 0.0077) were observed between 36-45 and >55 years group. Conclusions: ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients ≤55 years old is key to improved diagnostic rate.

Background: Early screening for colorectal cancer (CRC) has the potential to improve patient prognosis, but current screening methods are limited. In this prospective study, we aimed to evaluate the multigene (Septin9, SDC2, KCNQ5, and IKZF1) detection in patient plasma for CRC diagnosis. Methods: Overall, 67 participants were enrolled, including 31 patients with CRC, 17 patients with colorectal polyp, and 19 normal controls who underwent colonoscopy. Carcinoembryonic antigen (CEA) and Septin9, SDC2, KCNQ5, and IKZF1 methylation tests were performed. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of each biomarker. The association between positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed. Results: The positive rate of multigene methylation detection was 87.1% (27/31) in patients with CRC, which was higher than single indicators: CEA (51.61%, 16/31), Septin9 (41.94%, 13/31), SDC2 (41.94%, 13/31), KCNQ5 (58.06%, 18/31), and IKZF1 (32.26%, 10/31). In the colorectal polyp group, the rate of multigene methylation detection is 88.24% (15/17), which was also higher than single indicator: CEA (17.65%, 3/17), Septin9 (11.76%, 2/17), SDC2 (64.71%, 11/17), KCNQ5 (58.82%, 10/17), and IKZF1 (35.29%, 6/17). The ROC curves further showed better diagnostic value of the multigene test for CRC than any single gene. Correlation analysis found that the positive rate of the test was not affected by patients' clinicopathologic characteristics. Conclusion: The combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 tests is preferable to individual gene tests for patients with CRC and polyp.

Introduction: Expression of the nonclassical human leukocyte antigen (HLA)-G gene is upregulated in placenta during pregnancy. In other cells, HLA-G is upregulated during parasitic infections and allergic reactions. Polymorphism at the HLA-G gene locus has been reported for many populations, but so far not for any ethnic groups in Malaysia. In this survey, we screened for genetic variation in HLA-G genes from representative Malay, Chinese, and Indian individuals living in Peninsular Malaysia. Materials and Methods: Blood samples were obtained with informed consent, and ethnicity classes were assigned based on self-declared pedigree information. Exons 2, 3, and 4 of the HLA-G gene were amplified by polymerase chain reaction and subjected to Sanger sequencing. Results: The most common genotype in Malays and Indians was found to be HLA-G*01:01:01:01/01:01:01:01 with frequencies of 0.206 and 0.167, respectively, whereas the HLA-G*01:01:03:01/01:01:01:01 genotype was the one most frequently observed in Chinese (0.221). Based on this study, HLA-G*01:01:01:01 (0.427-0.448) is the most frequent HLA-G allele in the all three ethnic groups. In contrast, HLA-G*01:01:02:01 (0.186) was observed as the second most frequent HLA-G allele in Malays and HLA-G*01:04:01 in Chinese and Indians, (0.188-0.198, respectively). Several minor HLA-G alleles were detected at low frequency in Malays, Chinese, or Indians (HLA-G*01:01:05, 01:01:09, 01:04:02, and 01:04:03). These have only rarely, if ever, been reported in other population groups. Subsequent statistical analysis including using principal coordinate data mapping showed the Malays, Chinese, and Indians are distinct but quite closely related to one another as compared with other population groups from across Europe and Africa. Conclusion: The HLA-G population data collected in this study showed that the ancestrally unrelated Malays, Chinese, and Indians are genetically distinct. This new database provides a foundation for further studies to capture HLA-G allelic diversity in uncharacterized populations of Malaysia and for future attempts to identify their roles in disease resistance and susceptibility.

Background: Earlier research has demonstrated a genetic basis for the susceptibility to ankylosing spondylitis (AS) and the severity of AS. By employing a genome-wide association study, recent work has established a correlation between the susceptibility to AS and the ANO6, HAPLN, and EDIL3 genes in a Western study population-though alternative studies have not corroborated these findings. This study aims to examine the effects of ANO6, HAPLN1, and EDIL3 polymorphisms on the susceptibility and severity of AS among the predominantly Chinese Han population. Methods: The study involved the collection of blood samples from 497 patients with AS and 498 nonrelated healthy individuals. All participants in the study were human leukocyte antigen (HLA) HLA-B27 positive and of Han Chinese descent. Illness severity was the criteria used for classifying patients with AS. Thirteen tagSNPs in ANO6, HAPLN1, and EDIL3 were chosen and then subjected to genetic typing. Analysis was conducted on the occurrence rates of various genotypes and alleles between the control group and patients with varying AS severity. Results: Following Bonferroni correction, it was found that the rs4768085 and rs17095830 single nucleotide polymorphism (SNPs) in ANO6 were related to the susceptibility to AS. Further, the rs6869296 SNP in HAPLN1 and the rs2301071 SNP between EDIL3 and HAPLN1 were also related to AS susceptibility. Regarding AS severity, the rs4768085, rs2897868, rs7965430, and rs11182965 SNPs in ANO6 were found to be associated. Conclusions: Among the Han population in China, the ANO6 and HAPLN1 genes are related to the susceptibility to AS; the ANO6 gene is also associated with the severity of AS.