Objective To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR. Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98％ and 11.01％ respectively, which were both higher than that in controls (2.30％, P<0.05). The methylation rates in remission AML and ALL were 1.58％and 2.30％respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26％ and 17.50％respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00％, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56％. The median methylation rate in patients with MDS significantly elevated as 5.81％ compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months) (P<0.05). The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M3) patients. Conclusion ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.

OBJECTIVE: To explore the molecular basis for an A subtype of the ABO blood group. METHODS: The forward and reverse typing of the ABO blood group were identified by gel card and test tube methods. The ABO gene of the patient was detected by PCR-sequence specific primer (PCR-SSP). Exons 1 to 7 of the ABO gene was amplified by PCR and sequenced. The ABO gene was also subjected to subclone sequencing for haplotype analysis. RESULTS: The patient's red cells showed weak agglutination with anti-A but non-agglutination with anti-B. The patient's serum showed 1+ agglutination with A cells and 4+ agglutination with B cells. Based on above serological characteristics, the patient was defined as Aw subtype of the ABO blood group. Sequencing analysis showed that the patient was heterozygous for c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.297A>G, c.467C>T, c.543G>C, c.646T>A, c.681G>A, c.771C>T, c.829G>A, in addition with a c.261G deletion. Combined with the result of subclone sequencing, the ABO genotype of the patient was determined as ABO*AW.33. new/O.01.02, which harbored c.467C>T and c.543G>C variants compared with ABO*A1.01 and c.543G>C variant compared with ABO*A1.02. The novel allele has been submitted to GenBank with an accession number of MK302122. CONCLUSION A novel allele of Aw33 subtype has been identified with its GTA transferase gene harboring c.467C>T and c.543G>C variants compared with A1.01.
ABO Blood-Group System ; genetics ; Alleles ; Exons ; genetics ; Genotype ; Humans ; Phenotype

Objective: To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis. Methods: A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method. Results: A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m². Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (β=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (β=0.04, P=0.007) and closely related to cg15053022 (F=237.66, P=0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (β=-1.97, P<0.001). Conclusion This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.

Objective:To research the association between exposure to solid fuels for heating and its duration and the risk of respiratory diseases morbidity.Methods:Data from the China Kadoorie Biobank project sited in Pengzhou City, Sichuan Province. Cox proportional hazard regression model was used to analyze the association between exposure to solid fuels for heating and its duration and the risk of total respiratory diseases and the association between exposure to solid fuels for heating and the risk of chronic obstructive pulmonary disease (COPD) and pneumonia among respiratory diseases.Results:A total of 46 082 participants aged 30-79 years were enrolled, with 11 634 (25.25%) heating during the winter, of whom 8 885 (19.28%) used clean fuels and 2 749 (5.97%) used solid fuels, of whom 34 448 (74.75%) did not heat. After controlling for multiple confounding factors, Cox proportional hazard regression model was used, which revealed that compared with clean fuels, unheating could reduce the risk of total respiratory disease ( HR=0.81,95% CI:0.77-0.86), COPD ( HR=0.86,95% CI:0.78-0.95) and pneumonia ( HR=0.80,95% CI:0.74-0.86), respectively. Exposure to solid fuels increased the risk of total respiratory disease ( HR=1.10, 95% CI:1.01-1.20) and were not associated with COPD and pneumonia. Compared with no solid fuel exposure, the risk of total respiratory disease (1-19 years: HR=1.23, 95% CI:1.10-1.37; 20-39 years: HR=1.25, 95% CI:1.16-1.35; ≥40 years: HR=1.26, 95% CI:1.15-1.39) and COPD (1-19 years: HR=1.21, 95% CI:1.03-1.42; 20-39 years: HR=1.30, 95% CI:1.16-1.46; ≥40 years: HR=1.35, 95% CI:1.18-1.54) increased with the length of exposure of solid fuels (trend test P<0.001). Solid fuels exposure for 1-19 years and 20-39 years increased the risk of COPD by 23% ( HR=1.23,95% CI:1.02-1.49) and 16% ( HR=1.16, 95% CI:1.00-1.35). Conclusion:Heating solid fuels exposure increases the risk of total respiratory disease, COPD, and pneumonia.

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.

Objective:To explore clinical value of nucleic acid detection for hepatitis B virus (HBV) screening in hospitalized patients.Methods:This cross-sectional study collected and analyzed plasma samples from patients admitted to 10 domestic medical institutions from July 2021 to December 2021. Serological immunoassay and nucleic acid screening were used to simultaneously detect hepatitis B markers such as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e Antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb),and HBV DNA. Statistical analysis was performed on the serology, nucleic acid test results and clinical information of the patients.Results:Of the 8 655 collected samples, HBsAg was positive in 216 (2.50%) samples,HBV DNA was positive in 238 (2.75%) samples ( P>0.05); 210 (2.43%) samples were positive for both HBsAg and HBV DNA, 28 (0.32%) were HBsAg negative and HBV DNA positive, 6 cases (0.07%) were HBsAg positive and HBV DNA negative. Conclusion:These results indicate that the HBV DNA testing is equally effective as hepatitis B virus serological detection for hepatitis B virus screening in hospitalized patients.

Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.

Objective:To quantitate the association between birth weight and phenotypes of physical indicators in adulthood, i.e. BMI and waist circumference (WC) and to what degree genetic or environmental factors affect birth weight-obesity association.Methods:A total of 6 623 gender matched twin pairs aged 25 to 79 years were recruited through the Chinese National Twin Registry. The twins reported their own birth weight, current height and weight, and WC using a self-administered questionnaire. BMI was calculated according to the self-reports of body height and weight. Within twin-pair design was used to quantitate the association between birth weight and phenotypes related to obesity while bivariate structural equation models were used to decompose the phenotype correlation.Results:After adjusted for multiple factors, twin-pair analyses within monozygotic (MZ) showed that, on average, a 1.0 kg increase in birth weight corresponded to an increase of 0.33 kg/m 2 in BMI and 0.95 cm in WC in adulthood ( P<0.001). Bivariate structural equation models showed significant positive unique environmental correlation between birth weight and the two obesity-related phenotypes. Conclusion:The study supported the role of twin-specific supply line factors on relationship between birth weight and physical indicators in adulthood.

Objective:To analyze the heritability of coronary heart disease (CHD) among the Chinese twin adults.Methods:A total of 20 477 same-sex twin pairs aged 25 years and older from the Chinese National Twin Registry were interviewed. Structure equation model was used to estimate the heritability of CHD.Results:After adjusting for age and gender, the overall heritability of CHD was 0.75(0.68-0.81). Stratified analyses showed that genetic factors play a more important role in CHD incidence in ≥40 years or female twins. While the development of CHD was mainly influenced by environmental factors in 25-39 years or male twins.Conclusion:CHD is influenced by both genetic and environmental factors and the heritability is high.

Objective:To explore the genetic and environmental effects on alcohol intake.Methods:Data on 9 231 pairs of adult twins of the same sex was collected from the Chinese National Twin Registry (CNTR), between 2015 and 2018 and used in this study. Structural equation model was used to estimate the effects of genetic and environmental factors on alcohol intake.Results:A total of 9 231 pairs of twins were included in the analysis, of which 6 085 pairs were monozygotic (MZ). The average age of MZ was (36.91±13.07) years old, and males accounted for 56.80 %. The average age of dizygotic twins (DZ) was (35.22±12.48) years old, and males accounted for 55.91 %. There were 350 pairs of alcohol-drinking twins were with high-risk, accounting for 1.90 % and another 367 pairs (1.99 %) were with medium-risk. Alcohol-drinkers with medium-risk were affected by additive genetics, common and unique environmental factors, seen among the twins. The overall heritability appeared as 24.3 % (95 %CI: 0 to 56.8 %). Furthermore, 50.7 % of the variation (95 %CI: 20.4 %-79.0 %) could be explained by the common environmental factors and 24.9 % (95 %CI: 18.3 %-36.5 %) by unique environmental factors. High-risk related drinking behavior was affected by both common and unique environmental factors. The common environmental component appeared as 75.6 % (95 %CI: 69.6 %-80.8 %) and unique environmental component as 24.4 % (95 %CI: 19.2 %-30.4 %), respectively. Gender difference was seen in the heritability of those with medium or high-risk drinking behaviors. The heritability of men was 30.8 % (95 %CI: 9.8 %-53.5 %), while in women it was mainly affected by the environment. Conclusion:Both alcohol drinkers with medium and high-risk drinking behaviors were mainly affected by the environment factors and gender. With the increase of drinking volume, the effect of environment on drinking behaviors became more obvious.