Immunoglobulin G N-glycan, inflammation and type 2 diabetes in East Asian and European populations: A Mendelian randomization study

Background: Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. Methods: We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry). Results: After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95 % CI = 1.003–1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95 % CI = 1.006–1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95 % CI: 0.845 – 0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias. Conclusions: Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D

First age- and gender-matched case-control study in Australia examining the possible association between toxoplasma gondii Infection and type 2 diabetes mellitus: The Busselton Health Study

An emerging field of research is starting to examine the association of infectious pathogens with type 2 diabetes mellitus (T2DM). An understudied parasite of interest is Toxoplasma gondii. Globally, very few studies have been conducted to investigate this association. Additionally, very little data exists on the prevalence of T. gondii in the general Australian population. Our group sought to determine the prevalence, association, and risk factors between T. gondii infection and T2DM from a representative Australian human population. Through a cross-sectional, age-A nd gender-matched case-control study, 150 subjects with T2DM together with 150 control subjects from the Busselton Health Study cohort were investigated. Sera samples were tested for the presence of anti-T. gondii IgG and IgM antibodies using enzyme-linked immunosorbent assays. Survey-derived data were also analyzed to evaluate associated risk factors. The IgG seroprevalence was found to be 62% and 66% for the T2DM and control groups, respectively (OR:0.84; p=0.471). IgM antibodies were detected in 5% of the T2DM patients and in 10% of the controls (OR=0.51; p=0.135). There were no significant differences between male and female IgG seroprevalence rates for both groups (OR:0.88, 0.80; p=0.723). The IgG seropositivity rate increased significantly in T2DM patients aged 45-84 years in comparison to those aged 18-44 years (p\u3c 0.05), but this was not observed in the control subjects. No risk factors were associated with T. gondii seropositivity in both groups. The first Australian study of its kind found T. gondii infection in Western Australia to be highly prevalent. The results also showed that there is no serological evidence of an association between T. gondii infection and T2DM in the studied subjects. Australian health authorities should focus on raising awareness of toxoplasma infection and target T. gondii transmission control. Further studies are needed to clarify the role of T. gondii in T2DM. © 2020 Aus Molan et al

Development of a medical academic degree system in China

Context: The Chinese government launched a comprehensive healthcare reform to tackle challenges to health equities. Medical education will become the key for successful healthcare reform. Purpose:We describe the current status of the Chinese medical degree system and its evolution over the last 80 years. Content: Progress has been uneven, historically punctuated most dramatically by the Cultural Revolution. There is a great regional disparity. Doctors with limited tertiary education may be licensed to practice, whereas medical graduates with advanced doctorates may have limited clinical skills. There are undefined relationships between competing tertiary training streams, the academic professional degree, and the clinical residency training programme (RTP). The perceived quality of training in both streams varies widely across China. As the degrees of master or doctor of academic medicine is seen as instrumental in career advancement, including employability in urban hospitals, attainment of this degree is sought after, yet is often unrelated to a role in health care, or is seen as superior to clinical experience. Meanwhile, the practical experience gained in some prestigious academic institutions is deprecated by the RTP and must be repeated before accreditation for clinical practice. This complexity is confusing both for students seeking the most appropriate training, and also for clinics, hospitals and universities seeking to recruit the most appropriate applicants. Conclusion: The future education reforms might include: 1) a domestic system of \u27credits\u27 that gives weight to quality clinical experience vs. academic publications in career advancement, enhanced harmonisation between the competing streams of the professional degree and the RTP, and promotion of mobility of staff between areas of excellence and areas of need; 2) International - a mutual professional and academic recognition between China and other countries by reference to the Bologna Accord, setting up a system of easily comparable and well-understood medical degrees

The Expected Number of Background Disease Events during Mass Immunization in China

It is critical to distinguish events that are temporarily associated with, but not caused by, vaccination from those caused by vaccination during mass immunization. We performed a literature search in China National Knowledge Infrastructure and Pubmed databases. The number of coincident events was calculated based on its incidence rate and periods after receipt of a dose of hypothesized vaccine. We included background incidences of Guillain-Barre´ syndrome, anaphylaxis, seizure, sudden adult death syndrome, sudden cardiac death, spontaneous abortion, and preterm labour or delivery. In a cohort of 10 million individuals, 7.71 cases of Guillain-Barre´ syndrome would be expected to occur within six weeks of vaccination as coincident background cases. Even for rare events, a large number of events can be expected in a short period because of the large population targeted for immunization. These findings may encourage health authorities to screen the safety of vaccines against unpredictable pathogens

Influence of brain-derived neurotrophic factor genetic polymorphisms on the ages of onset for heroin dependence in a Chinese population

Aim: The study aims at evaluating the association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and heroin-dependent patients in the Chinese population. Three polymorphisms of the BDNF-gene (rs10835210, rs16917234, and rs6265) in 486 heroin-dependent patients and in 226 healthy controls were genotyped for analyzing the association of these polymorphisms with age of onset of heroin dependence. We defined the healthy cases as “unknown phenotype” and used the endophenotype (behavior traits) to stratify the heroin dependents group on the basis of self-reporting traits for examining the association between BDNF polymorphisms (rs10835210, rs16917234, and rs6265) and heroin dependence. Results: Allelic distributions of BDNF gene polymorphisms did not differ significantly between heroin-dependent patients and controls. However, we found that the AA carriers of BDNF rs6265 had an earlier onset of heroin dependence and a clearer tendency of family history of heroin-dependent than GG carriers after controlling behavior characteristics across rs6265 genotypes. Conclusions: Our findings suggested that the BDNF genetic polymorphism (rs6265) may have effects on the age of onset of heroin dependence among the Chinese population. The BDNF gene could contribute to vulnerabilities to heroin dependence

The genetic contribution of CIDEA polymorphisms, haplotypes and loci interaction to obesity in a Han Chinese population

To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case-control study. Genotyping was performed using the sequenom matrixassisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P\u3e0.001), SNP1 (P = 0.006) and SNP2 (P = 0.005). Carriers of V115F-TT, SNP1-GG and SNP2-CC genotypes had a 2.84-fold (95 % CI 1.73-4.66), 2.19-fold (95 % CI 1.09-4.38) and 4.37-fold (95 % CI 1.21-15.08) increased risk for obesity, respectively. Haplotype analysis showed that GTTC (SNP1/ SNP2/V115F/SNP4) had 1.41-fold (95 % CI 1.02-1.95) increased risk for obesity; whereas, haplotype TTGC had 0.48-fold (95 % CI 0.24-0.96) decreased risk for obesity. Using the multifactor dimensionality reduction method, the best model including SNP1, SNP2, V115F and SNP4 polymorphisms was identified with a maximum testing accuracy to 59.32 % and a perfect cross-validation consistency of 10/10 (P = 0.011). Logistic analysis indicated that there was a significant interaction between SNP1 and V115F associated with obesity. Subjects having both genotypes of SNP1/GG and V115F/TT were more susceptible to obesity in the Han Chinese population (OR 2.66, 95 %: 1.22-5.80). Genotypes of V115F/TT, SNP1/ GG and SNP2/CC and haplotype GTTC of CIDEA gene were identified as risk factors for obesity in the Han Chinese population. The interaction between SNP1 and V115F could play a joint role in the development of obesity

Association between ideal cardiovascular health metrics and suboptimal health status in Chinese population

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30% women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10%, 9.18%, 10.04% and 10.62% in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32–0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases

Association between ideal cardiovascular health metrics and suboptimal health status in Chinese population

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30 % women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10 %, 9.18 %, 10.04 % and 10.62 % in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32 – 0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases

Bidirectional causality between immunoglobulin G N-glycosylation and metabolic traits: A mendelian randomization study

Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P \u3c 0.05). Accordingly, in the reverse MR analysis of the integrated metabolic-QTL variants with the GWAS results for IgG N-glycosylation traits, 72 (including one putatively causal metabolic trait for GP1 (high-density lipoprotein cholesterol (HDL-C)) and five for GP2 (FPG, systolic blood pressure (SBP), etc.)) and four (including one putatively causal metabolic trait for GP3 (HDL-C) and one for GP9 (HDL-C)) genetically determined metabolic traits were found to be related to the risk of IgG N-glycosylation in one- and two-sample MR studies, respectively (all P \u3c 0.05). Notably, genetically determined associations of GP11 BMI (fixed-effects model-Beta with standard error (SE): 0.106 (0.034) and 0.010 (0.005)) and HDL-C GP9 (fixed-effects model-Beta with SE: –0.071 (0.022) and –0.306 (0.151)) were identified in both the one- and two-sample MR settings, which were further confirmed by a meta-analysis combining the one- and two-sample MR results (fixed-effects model-Beta with 95% confidence interval (95% CI): 0.0109 (0.0012, 0.0207) and –0.0759 (–0.1186, –0.0332), respectively). In conclusion, the comprehensively bidirectional MR analyses provide suggestive evidence of bidirectional causality between IgG N-glycosylation and metabolic traits, possibly revealing a new richness in the biological mechanism between IgG N-glycosylation and metabolic traits. © 2022 THE AUTHOR