OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.
Humans ; Parkinson Disease/metabolism* ; alpha-Synuclein/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Genetic Predisposition to Disease ; Protein Kinases/genetics* ; Animals ; Glucosylceramidase/genetics* ; Ubiquitin-Protein Ligases/genetics*

Pancreatitis is an inflammatory disease influenced by both environmental and genetic factors. It has a high prevalence and mortality rate worldwide, with no radical cure. Breakthroughs have been recently made in genetic research of pancreatitis. Susceptibility genes and pathways have been continuously discovered, which highlighted the roles of genetic factors in hypertriglyceridemic and chronic pancreatitis. Gene therapy may offer radical cure for pancreatitis, though it has remained at the research phase. This article has reviewed the genetic pathogenesis of pancreatitis and current status of gene therapy research, with an aim to provide a reference for attaining definitive cure for the disease.
Humans ; Genetic Therapy/methods* ; Pancreatitis/etiology* ; Genetic Predisposition to Disease ; Animals

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of interleukin-23 receptor (IL-23R) gene with susceptibility to psoriasis. METHODS: Two hundred and ten psoriasis patients admitted to Xinxiang Central Hospital from January 2019 to December 2024 were selected as the study group, and 210 healthy individuals undergoing physical examination during the same period were selected as the control group. 3 mL of peripheral venous blood sample was collected from each individual from the two groups, and PCR-Restriction fragment length polymorphism (PCR-RFLP) assay was used to determine the polymorphisms of the IL-23R gene at rs2201841, rs1004819, rs10889677, rs1343151 and rs1495965 loci. Genotypic and allelic distribution of each SNP locus was calculated to assess the association between SNPs of the IL-23R gene with the onset of psoriasis, and the difference in serum IL-23 levels among patients with different genotypes at each locus was compared. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethic No. 2024-749). RESULTS: The results showed that the frequency of CC genotype at rs1004819 locus of the study group was significantly higher than that of the control group (26.19% vs. 18.10%, P < 0.05), and the frequency of C allele was also significantly higher than that of the control group (54.05% vs. 42.62%, P < 0.05). There was no significant difference in allelic and genotypic frequencies between the two groups at rs2201841, rs10889677, rs1343151, and rs1495965 loci (P > 0.05). The dominant and recessive inheritance patterns at the rs1004819 locus are associated with susceptibility to psoriasis (P < 0.05), while the different inheritance patterns at rs2201841, rs10889677, rs1343151, and rs1495965 loci are not associated with psoriasis (P > 0.05). The serum IL-23 levels of patients with CC genotype at the rs1004819 locus were higher than those with the CT and TT genotypes (P < 0.05). No significant difference was detected in the serum levels of IL-23 between patients with different genotypes for the rs2201841, rs10889677, rs1343151, and rs1495965 loci (P > 0.05). CONCLUSION The polymorphism at the rs1004819 locus of the IL-23R gene is associated with susceptibility to psoriasis, and individuals carrying the CC genotype and C allele have a higher risk of developing the disease.
Humans ; Psoriasis/genetics* ; Polymorphism, Single Nucleotide ; Receptors, Interleukin/genetics* ; Genetic Predisposition to Disease ; Male ; Female ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Case-Control Studies ; Interleukin-23/blood*

OBJECTIVE: To explore the association between single nucleotide polymorphism (SNP) rs2073618 and rs3102735 of the TNFRSF11B gene and the susceptibility to gastric cancer. METHODS: A case-control study was conducted. A total of 577 patients with primary gastric cancer treated at Zhenjiang First People's Hospital from May 2013 to June 2017 were selected as the case group, and 678 healthy individuals who underwent physical examinations at the same hospital during the same period were enrolled as the control group. Blood samples were collected from both groups, and genomic DNA was extracted. The target gene fragments were amplified using PCR, and genotyping was performed using the Snapshot technique. Statistical analysis was conducted using SPSS v2.0 software. This study was approved by the Medical Ethics Committee of the Zhenjiang First People's Hospital (Ethics No. 20150083). RESULTS: The smoking rate was significantly higher in the case group than in the control group (P = 0.006). The T>C polymorphism at the rs3102735 locus of the TNFRSF11B gene was significantly associated with an increased risk of gastric cancer (CC vs. TT: OR = 2.164, 95%CI = 1.063~4.406, P = 0.030). In contrast, the rs2073618 polymorphism did not show a significant association with gastric cancer susceptibility (P > 0.05). Stratified analysis by age, gender, smoking status, and drinking status revealed no significant association between the rs2073618 polymorphism and gastric cancer susceptibility (P > 0.05). However, the rs3102735 polymorphism showed a significant association with gastric cancer risk in individuals over 62 years of age (CC vs. TT: OR = 5.44, 95%CI = 1.54~19.21, P = 0.003). CONCLUSION The rs3102735 polymorphism of the TNFRSF11B gene may be associated with susceptibility to gastric cancer, particularly in older populations. This polymorphism could serve as a potential indicator for identifying high-risk groups for gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Polymorphism, Single Nucleotide ; Male ; Female ; Genetic Predisposition to Disease ; Middle Aged ; Case-Control Studies ; Osteoprotegerin/genetics* ; Aged ; Adult ; Genotype

OBJECTIVE: To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 (CYP19A1) gene with risk of Breast cancer. METHODS: Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No. 2021-182). RESULTS: No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups (P > 0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group (P < 0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages III-IV were significantly higher than those at stage I-II (P < 0.05). CONCLUSION Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
Humans ; Female ; Breast Neoplasms/genetics* ; Aromatase/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Middle Aged ; Genetic Predisposition to Disease ; Adult ; Genotype ; Case-Control Studies ; Alleles ; Gene Frequency ; Risk Factors ; Aged

OBJECTIVE: To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). METHODS: A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). RESULTS: The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). CONCLUSION The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect.
Humans ; Female ; Pregnancy ; Fatty Acid Desaturases/genetics* ; Polymorphism, Single Nucleotide ; Adult ; Diabetes, Gestational/blood* ; Blood Pressure/genetics* ; Lipids/blood* ; Genotype ; Genetic Predisposition to Disease

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of the cell division cycle 42 (CDC42) gene with Pulmonary artery systolic pressure (PASP) among patients with Congenital heart disease (CHD). METHODS: In this observational study, clinical data and blood samples were collected from 579 CHD patients with left-to-right shunt who presented to our hospital between January 2012 and January 2017. SNPs of the CDC42 gene were genotyped using an improved multiple ligase detection reaction. Multiple linear regression was applied to evaluate the association of CDC42 gene variants with PASP. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Ethics No.: 20180222-102). RESULTS: Polymorphisms at rs2501256 and rs34896897 of the CDC42 gene were significantly associated with PASP. Compared with the CC genotype at rs2501256, TT and CT carriers displayed higher PASP [TT vs. CC: B (95%CI) = 4.01 (1.95, 6.07), P < 0.001; CT vs. CC: B (95%CI) = 2.91 (0.63, 5.19), P < 0.001]. Similarly, GG and GA genotypes at rs34896897 were associated with higher PASP compared to the AA genotype [GG vs. AA: B (95%CI) = 26.15 (20.45, 31.84), P < 0.001; GA vs. AA: B (95%CI) = 7.19 (4.31, 10.08), P < 0.001]. Genetic model analyses demonstrated significant differences for both rs2501256 and rs34896897 under dominant, additive, and recessive models (P < 0.05). TT carriers at rs2501256 exhibited larger left-and right-atrial diameters, whereas GG carriers at rs34896897 showed greater right-atrial and right-ventricular end-diastolic dimensions. Subgroup analyses revealed no association between rs2501256 and PASP in males, individuals younger than 18 years, Uyghur ethnicity, or those with ventricular septal defects. CONCLUSION CHD patients carrying the minor alleles of rs2501256 and rs34896897 in the CDC42 gene present higher incidence of PASP compared to those carrying the common alleles.
Humans ; Male ; Female ; Heart Defects, Congenital/physiopathology* ; Polymorphism, Single Nucleotide ; cdc42 GTP-Binding Protein/genetics* ; Adult ; Child ; Genotype ; Adolescent ; Child, Preschool ; Genetic Predisposition to Disease ; Pulmonary Artery/physiopathology*

Inherited conditions have implications not only for the individual affected but for the entire family. It is in this context that family communication of genetic risk information is important to understand. This paper aims to provide an overview of the construct of family communication of genetic risk and provide implications for healthcare providers. A search of relevant literature was done with electronic databases including PubMed, CINAHL, Embase, Scopus, and Web of Science. The findings from the literature were organized based on the Family Communication of Genetic Risk (FCGR) conceptual framework which highlights the attributes of the family communication of genetic risk process including influential factors, communication strategy, communication occurrence, and outcomes of communication. Healthcare providers need to understand how individuals share genetic risk with their family members so that appropriate support and interventions can be provided to them. This is especially important across countries, including the Philippines, as genetic services and testing move beyond the traditional medical genetics clinic to other medical specialties, a development where we would expect an increase in individuals and family members undergoing genetic evaluation and testing.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors