Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese.

BACKGROUND: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS: Genes related to lipolysis, redox reaction, and proliferation of islet ß-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

Association between Human Genetic Variants and the Vaginal Bacteriome of Pregnant Women.

The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level (P < 5 × 10-8) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota, Firmicutes, Lactobacillus, and Gardnerella vaginalis and the beta diversity weighted UniFrac (P < 1 × 10-5). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

Overt and occult hepatitis B infection after neonatal vaccination: mother-to-infant transmission and HBV vaccine effectiveness.

OBJECTIVES: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. METHODS: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. RESULTS: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. CONCLUSIONS: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

[Phylogenetic analysis of hepatitis E virus strains isolated from both human and swine in Anqing City].

OBJECTIVE: To determine the genotype and phylogenetic characteristics of hepatitis E virus (HEV) strains isolated from the human and swine in Anqing City. METHODS: Twenty seven sera from sporadic hepatitis E patients and 400 commercial swine bile samples were collected in Anqing City. According to the collection time, the bile samples were equally divided into 4 groups which were named group A, B, C and D respectively. Nested reverse transcription polymerase chain reaction (RT-PCR) and DNA sequencing technology were performed to obtain the DNA sequences of HEV RNA Open Reading Frame 2 (ORF2) (150 nt) for all the serum and bile samples. The sample sequences and prototype sequences from the GenBank were aligned and their nucleotide sequence identities were calculated. A phylogenetic tree constructed according to the Bayesian inference method was used to analyze the genotype and phylogenetic relationship between the human and swine HEV strains isolated in Anqing City. RESULTS: The male-to-female sex ratio of the patients was 2.86:1 and the average age was 56.78 years old. Sixteen out of 27 serum (59.26%) samples were HEV RNA positive. Human HEV strains isolated in Anqing City shared 74.75% - 82.99%, 75.26% - 83.64%, 72.77% - 80.57% and 88.03%-91.63% nucleotide sequence identities with prototype I, II, III and IV HEV strains respectively. HEV RNA was detected in 22 out of 400 bile samples (5.5%). The swine HEV detection rates for group A, B, C and D were 7.00%, 3.00%, 9.00% and 3.00% respectively, showing no significant difference among these groups (χ(2) = 5.20, P = 0.16). Swine HEV strains isolated in Anqing City shared 75.24% - 83.42%, 75.93% - 84.19%, 72.86% - 80.64% and 88.15% - 91.79% nucleotide sequence identities with prototype I, II, III and IV HEV strains respectively. Phylogenetic analysis revealed that all the HEV strains isolated from both the human and swine belonged to genotype IV and scattered in evolutionary branches without significant species aggregation. CONCLUSION: It's suggested that genotype IV HEV was the dominant genotype among the human and swine in Anqing City and probably transmitted between them in this area.

[Study on the prevalence and genotype of hepatitis E virus among commercial swine population in Eastern and Southern China].

OBJECTIVE: To determine the prevalence and genotype of hepatitis E virus (HEV) among commercial swine population in Eastern and Southern China. METHODS: Six hundred specimens of swine bile collected from 5 slaughterhouses in Eastern and Southern China from 2007 to 2009 were tested for HEV RNA using nested RT-PCR. PCR products were sequenced for phylogenetic analysis. RESULTS: Forty-seven out of the 600 samples (7.83%) were positive for HEV RNA. Based on the 150 nt fragment within HEV ORF2, data from phylogenetic analysis revealed that all the 47 HEV isolates were identified to be genotype IV, sharing 75.0% - 83.4%, 75.0% - 84.6%, 71.9% - 80.7% and 88.1% - 91.5% nucleotide identities with prototype I, II, III and IV HEV strains respectively while majority of the isolates clustered within their respective isolation sites. CONCLUSION: HEV was widespread in commercial swine population in Eastern and Southern China that raised a serious concern about the safety regarding the consumption of pork products.

[Seasonal pattern and phylogenetic analysis with human isolates of genotype-IV hepatitis E virus in swine herds, eastern China].

OBJECTIVE: To determine the seasonal prevalence of genotype-IV hepatitis E virus (HEV) in swine herds in Eastern China and explore the phylogenetic relationship between swine HEV and human HEV in the situation that zoonotic features of HEV had been confirmed. METHODS: From September 2007 to June 2008, a total of 1200 swine bile specimens were collected from three slaughter houses located in Zhejiang, Anhui and Jiangsu, the Eastern China, and detected for HEV RNA by using nested RT-PCR. The positive PCR products were sequenced. Then the swine HEV were phylogenetically determined with human HEV isolated in Eastern China. RESULTS: The positive rate for HEV RNA in swine herds was 4.5% totally. Significant differences of HEV detection were not observed among seasonal pattern (Sep - Oct: 6%, Dec - Jan: 4.33%, Mar - Apr: 4.33%, May - Jun: 3.33%) but in geographic distribution (Jiangsu: 6%, Anhui: 5%, Zhejiang: 2.5%). Regardless of isolation from different areas,swine and human genotype-IV HEV shared a high similarity. Phylogenetically, there were 80% - 100% and 96% - 100% identities within swine genotype-lV HEV at the nucleotide and amino acid levels respectively. Between swine HEV and human HEV, there were also similarities of 76% -99% and 95% - 100%. It was noted that some human and swine isolates were clustered with bootstrap values of > 90%. CONCLUSION: Genotype-IV HEV is widely prevalent in swine herds in Eastern China and original common ancestor of evolution and transmission was implied. The sustaining prevalence within swine herds should have a probable influence on the epidemic situation of hepatitis E in human beings.

[Phylogenetic analysis of sporadic hepatitis E virus in Eastern China].

OBJECTIVE: To understand phylogenetic characteristics of sporadic hepatitis E virus (HEV) in eastern China. METHODS: Four hundred and thirteen sera were collected from sporadic hepatitis E cases in 14 second- or first-class hospitals in Eastern China from 2005 to 2008 and detected with a nested RT-PCR assay. Partial nucleotide sequences of the HEV isolates were determined for phylogenetic analysis with prototype sequences in the GenBank. RESULTS: The male-to-female sex ratio of the patients was 1.75:1 with 61.5% of them aged 40 - 69 years old. HEV RNA was detected in 140 out of 413(34%)serum samples. Phylogenetic analysis revealed that all the 140 HEV isolates belonged to genotype IV, sharing 77.9% - 88.3%, 80.8% - 90.6%, 73.4% - 85.2% and 91.0% - 95.4% nucleotide sequence identities with prototype I, II, III and IV HEV isolates respectively. CONCLUSION: It was evident that genotype IV HEV served as the main causative agent of sporadic HEV infection in Eastern China. However the viral origin and evolution needs further clarification.