Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population. METHODS: The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL. RESULTS: Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL. CONCLUSIONS: The CD40 gene may play a role in the occurrence and development of CSCC.

Corrigendum: Association between GSDMB gene polymorphism and cervical cancer in the Northeast Chinese Han population.

[This corrects the article DOI: 10.3389/fgene.2022.860727.].

GCKR and ADIPOQ gene polymorphisms in women with gestational diabetes mellitus.

AIMS: To investigate the associations of GCKR and ADIPOQ variants with the risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS: GCKR rs1260326, ADIPOQ rs266729, and rs1501299 were selected and genotyped in 519 GDM patients and 498 controls. Candidate SNPs were genotyped using multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods, and the association of these SNPs with GDM was analyzed. RESULTS: We found that GCKR rs1260326 was significantly associated with an increased risk of GDM in the allele model, the codominant model (CC vs. TT), the dominant model, the recessive model, and the genotypic model distributions (p = 0.0029, p = 0.0022, p = 0.0402, p = 0.0038, and p = 0.0028, respectively). The rs1260326 polymorphism was shown to be associated with 1 h-OGTT level and gravidity in GDM patients (CC vs. TT: p = 0.0475 and p = 0.0220, respectively). Diastolic blood pressure (DBP) was significantly higher in the GDM patients with the rs266729 GG genotype compared to those with the CC or CG genotype (p = 0.0444 and p = 0.0339, respectively). The DBP of the GDM patients with the rs1501299 GT genotype was lower than that of those with the GG genotype (p = 0.0197). There was a weak linkage disequilibrium value between the GCKR and ADIPOQ SNPs. CONCLUSIONS: The genes GCKR and ADIPOQ may be involved in the pathophysiology of GDM.

Association Between GSDMB Gene Polymorphism and Cervical Cancer in the Northeast Chinese Han Population.

Objective: The purpose of this study was to investigate the relationship between GSDMB gene polymorphism and genetic susceptibility to cervical cancer in the Han population in Northeast China. Methods: In this case-control study, the genotypes and alleles of rs8067378 in the GSDMB gene were analyzed by multiplex polymerase chain reaction (PCR) and next-generation sequencing methods in 482 cervical cancer (CC) patients, 775 cervical squamous intraepithelial lesion (SIL) patients, and 495 healthy women. The potential relationships between the SNP of the GSDMB gene with SIL and CC were analyzed by multivariate logistic regression analysis combined with 10,000 permutation tests. Results: In the comparison between the SIL group and the control group, the genotype and allele distribution frequencies of rs8067378 SNP of the GSDMB gene were statistically significant (p = 0.0493 and p = 0.0202, respectively). The allele distribution frequencies of rs8067378 were also statistically significant in the comparison between high-grade cervical squamous intraepithelial lesion (HSIL) and low-grade cervical squamous intraepithelial lesion (LSIL) groups with control group ( p = 0.0483 and p = 0.0330, respectively). Logistic regression analysis showed that after adjusting for age, the rs8067378 SNP of the GSDMB gene was significantly associated with the reduced risk of SIL under the dominant model (p = 0.0213, OR = 0.764, CI = 0.607-0.961) and the additive model (p = 0.0199, OR = 0.814, and CI = 0.684-0.968), and its mutant gene G may play a role in the progression of healthy people to LSIL and even HSIL as a protective factor. However, there was no significant association between cervical cancer and its subtypes with the control group (p > 0.05). After 10,000 permutations, there was still no correlation that has provided evidence for the accuracy of our study. Conclusion: The results of this study showed that rs8067378 single nucleotide polymorphism of the GSDMB gene may reduce the risk of SIL and protect the susceptibility to cervical precancerous lesions in the Northeast Chinese Han population, but it has no significant correlation with the progression of cervical cancer.

Single Nucleotide Polymorphisms of EXOC1, BCL2, CCAT2, and CARD8 Genes and Susceptibility to Cervical Cancer in the Northern Chinese Han Population.

Cervical cancer (CC) is one of the main malignant tumors that threaten the health and lives of women around the world, and its morbidity and mortality rate ranks fourth. At present, most studies on the genetic background of CC focus on genetic polymorphisms. Single nucleotide polymorphisms (SNPs) are considered clinically as potential diagnostic and therapeutic biomarkers for a variety of tumors. Therefore, we aimed to explore the association between SNPs in different genes (EXOC1 gene, BCL2 gene, CCAT2 gene and CARD8 gene) and susceptibility to CC. This study is a case-control study based on women in northern Chinese, which included 492 women with CC and 510 healthy women. This study used multiplex PCR combined with next-generation sequencing to genotype the selected SNPs (rs13117307(C/T) in EXOC1 gene, rs2279115(C/A) in BCL2 gene, rs6983267(G/T) in CCAT2 gene and rs7248320(G/A) in CARD8 gene). The results of the study showed that there was no significant association between the four SNPs and the susceptibility to CC. However, in further stratified analysis, we found that rs13117307 and rs2279115 were significantly related to squamous cell carcinoma antigen (SCC-Ag) levels in women with CC, and rs6983267 was significantly related to the menopausal status of women with CC. Specifically, alleles T of rs13117307 and genoytpe AA of rs2279115 when SCC-Ag is greater than 1.5 ng/ml increase the risk of CC. The genotype TG/TG+TT of rs6983267 increases the risk of CC in premenopausal women. In conclusion, although we did not directly find a significant correlation between four SNPs, rs13117307 in EXOC1 gene,rs2279115 in BCL2 gene, rs6983267 in CCAT2 gene and rs7248320 in CARD8 gene, and CC susceptibility, we found that SNPs rs13117307, rs2279115, rs6983267 were associated with the clinical characteristics of several patients' CC patients. Therefore, this study provides us with new ideas for understanding CC and the diagnosis and treatment of CC in the future.

An association study between MiR-146a and INSR gene polymorphisms and hypertensive disorders of pregnancy in Northeastern Han Chinese population.

INTRODUCTION: Hypertensive disorders of pregnancy(HDP) is a complex and challenging group of pregnancy complications that is one of the leading causes of maternal and fetal death worldwide. Recent studies have shown that the single nucleotide polymorphism(SNP) may play a role in the pathogenesis of HDP. This study aimed to investigate the association of MiR-146a rs2910164 and insulin receptor(INSR) rs2059806 SNPs with HDP and their associated complications in the Han population of Northeast China. METHODS: A total of 240 HDP patients and 380 healthy controls were selected for genotype determination. For the most special and high incidence of HDP, we also studied the SNPs in association with pre-eclampsia(PE) patients. In addition, HDP complicated with gestational diabetes mellitus(GDM) patients was further analyzed to identify the association between SNPs and HDP-related complications. Multivariate logical regression analysis combined with 10, 000 permutation test corrections was used to analyze the association of MiR-146a and INSR SNPs with HDP. RESULTS: After adjusting for relevant factors, MiR-146a rs2910164 or INSR rs2059806 SNPs were not significantly different between HDP or PE patients and healthy controls(P>0.05). Meanwhile, MiR146a rs2910164 and INSR rs2059806 SNPs were not significantly different between HDP complicated with GDM and control group. DISCUSSION: Our data indicates that MiR-146a rs2910164 and INSR rs2059806 SNPs may not be significantly related with HDP in the Han population of Northeast China living in Heilongjiang Province.