COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Genetic Linkage ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification*

PURPOSE: Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. MATERIALS AND METHODS: We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS: We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION: Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.
Exome ; Far East ; Female ; Genetic Variation ; Genome ; Genome-Wide Association Study ; Genotype ; Humans ; Incidence ; Linkage Disequilibrium ; Mortality ; Odds Ratio ; Prostate ; Stem Cells ; Stomach Neoplasms

OBJECTIVE: To assess the value of Karyomapping for the prenatal diagnosis of facioscapulohumerial muscular dystrophy type 1 (FSHD1). METHODS: Peripheral blood and chorionic villi samples were collected from five families affected with FSHD1. Linkage-based diagnosis was carried out by using the Karyomapping method. Diagnosis for two fetal samples was carried out with the next-generation optical mapping system. RESULTS: The results of Karyomapping showed that three fetuses inherited the risky 4q35 region of the proband and two fetuses did not. The fetuses of families 1 and 2 received further diagnosis by the next-generation optical mapping system, and the results were consistent with those of Karyomapping. CONCLUSION Karyomapping has enabled prenatal diagnosis for the five families affected with FSHD1. The method was faster and simpler compared with conventional strategies, though its feasibility still needs further validation. Since there were no SNP loci designed on the Karyomap chip for the DUX4 gene and its 3' flanking regions, misjudgment due to chromosomal recombination could not be completely eliminated. The accuracy of this method still needs further validation.
Female ; Genetic Linkage ; Humans ; Muscular Dystrophies ; Pregnancy ; Prenatal Diagnosis

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.
Alleles ; Child ; Enzyme-Linked Immunosorbent Assay ; Epilepsy ; Epilepsy, Generalized ; Fever ; Genetic Predisposition to Disease ; Genotype ; HMGB1 Protein ; Humans ; Inflammation ; Interleukin-1 ; Interleukin-6 ; Interleukins ; Linkage Disequilibrium ; Multigene Family ; Promoter Regions, Genetic ; Seizures ; Seizures, Febrile

To further enrich the genetic data of the Chinese Xinjiang Mongolian group, the genetic distribution and forensic parameters of 19 autosomal short tandem repeats (STRs) were investigated. Altogether, 249 alleles were observed in these 19 STRs. The mean values of the polymorphism information content (PIC), match probability (MP), discrimination power (DP), and probability of exclusion (PE) for these 19 STRs were 0.7775, 0.0699, 0.9301, and 0.6085, respectively. Additionally, the cumulative DP and PE values obtained in the Mongolian group were 0.999 999 999 999 999 999 999 995 67 and 0.999 999 992 163, respectively. Furthermore, population genetic analysis of the Mongolian group and 20 published populations was conducted based on the population data of 15 overlapping STRs. Genetic distances indicated that the Mongolian group had closer genetic similarities with the Uyghur, Xibe, and other Chinese populations rather than the other continental populations. Multidimensional scaling analysis further revealed that the Mongolian group possessed similar genetic distributions as most Chinese populations. To sum it all up, these STRs could be used as an extremely efficient tool for forensic applications in the Xinjiang Mongolian group.
Alleles ; Asian People/genetics* ; China ; DNA Fingerprinting ; Databases, Genetic ; Ethnicity/genetics* ; Gene Frequency ; Genetic Markers ; Genetics, Population ; Genome, Human ; Humans ; Linkage Disequilibrium ; Microsatellite Repeats ; Mongolia ; Polymorphism, Genetic ; Principal Component Analysis ; Probability ; Software

OBJECTIVE: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. METHODS: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis. RESULTS: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. CONCLUSIONS The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
Adaptor Proteins, Signal Transducing/genetics* ; Adult ; Aged ; Alleles ; Asian People ; Cardiomyopathy, Dilated/surgery* ; China/epidemiology* ; Defibrillators, Implantable ; Exons ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; LIM Domain Proteins/genetics* ; Linkage Disequilibrium ; Male ; Middle Aged ; Mutation ; Polymorphism, Genetic ; Sequence Analysis, DNA

Chinese ferret badger (FB)-transmitted rabies is a serious threat to public health in southeast China. Although mostly associated with dogs, the rabies virus (RABV) presents genetic diversity and has a significantly wide host range in China. Instead of the dog- and wildlife-associated China II lineage in the past decades, the China I lineage has become the main epidemic group hosted and transmitted by dogs. In this study, four new lineages, including 43 RABVs from FBs, have been classified within the dog-dominated China I lineage since 2014. FB RABVs have been previously categorized in the China II lineage. Moreover, FB-hosted viruses seem to have become the main independent FB-associated clade in the phylogenetic tree. This claim suggests that the increasing genetic diversity of RABVs in FBs is a result of the selective pressure from coexisting dog rabies. FB transmission has become complicated and serious with the coexistence of dog rabies. Therefore, apart from targeting FB rabies, priority should be provided by the appropriate state agencies to perform mass immunization of dog against rabies.
Animals ; Brain ; virology ; China ; epidemiology ; Disease Reservoirs ; veterinary ; virology ; Dog Diseases ; epidemiology ; transmission ; virology ; Dogs ; Ferrets ; virology ; Genetic Linkage ; Genetic Variation ; Phylogeny ; Phylogeography ; Rabies ; epidemiology ; transmission ; veterinary ; virology ; Rabies virus ; genetics

BACKGROUND/AIMS: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. METHODS: We performed a genome-wide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. RESULTS: After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p < 8.56×10⁻⁸) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p < 8.56×10⁻⁸). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p < 2.0×10⁻¹⁰ in the discovery set and p < 2.0×10⁻⁶ in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p < 2.0×10⁻¹⁰ in the discovery set and p < 2.0×10⁻⁶ in the validation set). CONCLUSIONS: We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD.
Alanine Transaminase ; Body Mass Index ; Fatty Liver ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium ; Non-alcoholic Fatty Liver Disease* ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called “6-month rule.” This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.
Alcohol Abstinence ; Alcoholics* ; Alcoholism ; Carcinoma, Hepatocellular ; Fibrosis ; Genetic Linkage ; Hepatitis, Alcoholic* ; Humans ; Liver Diseases, Alcoholic ; Liver Failure ; Liver Transplantation ; Liver* ; Mortality

Previous genome-wide association studies have identified variants in the diacylglycerol kinase kappa (DGKK) gene associated with hypospadias in populations of European descent. However, no variants of DGKK were confirmed to be associated with hypospadias in a recent Han Chinese study population, likely due to the limited number of single-nucleotide polymorphisms (SNPs) included in the analysis. In this study, we aimed to address the inconsistent results and evaluate the association between DGKK and hypospadias in the Han Chinese population through a more comprehensive analysis of DGKK variants. We conducted association analyses for 17 SNPs in or downstream of DGKK with hypospadias among 322 cases (58 mild, 113 moderate, 128 severe, and 23 unknown) and 1008 controls. Five SNPs (rs2211122, rs4554617, rs7058226, rs7063116, and rs5915254) in DGKK were significantly associated with hypospadias (P < 0.05), with odds ratios (ORs) of 1.64-1.76. When only mild and moderate cases were compared to controls, 10 SNPs in DGKK were significant (P < 0.05), with ORs of 1.56-2.13. No significant SNP was observed when only severe cases were compared to controls. This study successfully implicated DGKK variants in hypospadias risk among a Han Chinese population, especially for mild/moderate cases. Severe forms of hypospadias are likely due to other genetic factors.
Asian People ; Case-Control Studies ; Child ; China/epidemiology* ; Diacylglycerol Kinase/genetics* ; Genetic Predisposition to Disease/genetics* ; Genetic Variation/genetics* ; Genome-Wide Association Study ; Haplotypes ; Humans ; Hypospadias/genetics* ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide/genetics* ; Risk Assessment