Association between ABO Blood Groups and Type 2 Diabetes Mellitus:
A Meta-Analysis

Cano, Earl Adriane; Esguerra, Marion Agatha; Batausa, Ariane Michaela; Baluyut, Jessica Rose; Cadiz, Ria; Docto, Hewmy Franci; Encabo, Jose Ramir; Gomez, Reena Mae; Sadang, Maria Gina

doi:10.2174/1573399818666220427124448

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…The exact underlying mechanisms behind this connection remain unclear and are possibly ascribed to systemic inflammatory and immune response [ 65 – 67 ]. Interestingly, type 2 diabetes, a known risk factor for PC, was found to partially mediate the causal effect from ABO to PC in our study, despite the controversial association between blood group and diabetes in previous reports [ 68 , 69 ]. Similarly, a retrospective study revealed a higher proportion of B blood type patients among those with long-term diabetes before PC diagnosis than that among PC patients without diabetes at diagnosis [ 70 ], which also implied the intricate interaction between ABO blood type, diabetes mellitus, and PC.…”

Section: Discussioncontrasting

confidence: 58%

Integrating plasma protein-centric multi-omics to identify potential therapeutic targets for pancreatic cancer

Zhou,

Tao,

Guo

et al. 2024

J Transl Med

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Background Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment. Methods We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings. The causative effect of corresponding protein-coding genes’ expression and their expression pattern in single-cell types were then investigated. Enrichment analysis, between-protein interaction and causation, knock-out mice models, and mediation analysis with established PC risk factors were applied to indicate the pathogenetic pathways. These candidate targets were ultimately prioritized upon druggability and potential side effects predicted by a phenome-wide MR. Results Twenty-one PC-related circulating proteins were identified in the exploratory phase with no evidence for horizontal pleiotropy or reverse causation. Of these, 11 were confirmed in a meta-analysis integrating external validations. The causality at a transcription level was repeated for neutrophil elastase, hydroxyacylglutathione hydrolase, lipase member N, protein disulfide-isomerase A5, xyloside xylosyltransferase 1. The carbohydrate sulfotransferase 11 and histo-blood group ABO system transferase exhibited high-support genetic colocalization evidence and were found to affect PC carcinogenesis partially through modulating body mass index and type 2 diabetes, respectively. Approved drugs have been established for eight candidate targets, which could potentially be repurposed for PC therapies. The phenome-wide investigation revealed 12 proteins associated with 51 non-PC traits, and interference on protein disulfide-isomerase A5 and cystatin-D would increase the risk of other malignancies. Conclusions By employing comprehensive methodologies, this study demonstrated a genetic predisposition linking 21 circulating proteins to PC risk. Our findings shed new light on the PC etiology and highlighted potential targets as priorities for future efforts in early diagnosis and therapeutic strategies of PC.

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Section: Discussioncontrasting

confidence: 58%

Integrating plasma protein-centric multi-omics to identify potential therapeutic targets for pancreatic cancer

Zhou,

Tao,

Guo

et al. 2024

J Transl Med

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“…A comparative cross-sectional study, including 326 participants (163 T2DM patients and 163 age and sex-matched healthy individuals), confirmed the harmful association of blood group B with T2DM risks (OR = 1.96; 95% CI: 1.05, 3.65), compared with the non-B blood group [ 80 ]. A meta-analysis revealed blood group B was significantly associated with an increased risk of T2DM (RR = 1.05; 95% CI: 0.93, 1.18), compared with the non-B blood group [ 81 ]. Nevertheless, caution is warranted in interpreting the observed association between blood group B and T2DM risk.…”

Section: Discussionmentioning

confidence: 99%

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies

Liu,

Guo,

Xing

et al. 2024

BMC Med

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Background Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. Methods We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). Results The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger’s test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. Conclusions Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

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Disentangling shared genetic etiologies for kidney function and cardiovascular diseases

Qiao,

Yao,

Yuan

et al. 2024

Preprint

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Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with chronic kidney disease (CKD) identified as a significant risk factor. CKD is primarily monitored through the estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation. Although epidemiological and clinical studies have consistently demonstrated strong associations between eGFR and CVDs, the genetic underpinnings of this relationship remain elusive. Recent genome-wide association studies (GWAS) have highlighted the polygenic nature of these conditions and identified several risk loci correlating with their cross-phenotypes. Nonetheless, the extent and pattern of their pleiotropic effects have yet to be fully elucidated. We analyzed the most comprehensive GWAS summary statistics, involving around 7.5 million individuals, to investigate the shared genetic architectures and the underlying mechanisms between eGFR and CVDs, focusing on single nucleotide polymorphisms (SNPs), genes, biological pathways, and proteins exhibiting pleiotropic effects. Our study identified 508 distinct genomic locations associated with pleiotropic effects across multiple traits, involving 379 unique genes, notably L3MBTL3 (6q23.1), MMP24 (20q11.22), and ABO (9q34.2). Additionally, pathways such as stem cell population maintenance and the glutathione metabolism pathway were pivotal in mediating the relationships between these traits. From the perspective of vertical pleiotropy, our findings suggest a causal relationship between eGFR and conditions such as atrial fibrillation and venous thromboembolism. These insights significantly enhance our understanding of the genetic links between eGFR and CVDs, potentially guiding the development of novel therapeutic strategies and improving the clinical management of these conditions.

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Association between ABO Blood Groups and Type 2 Diabetes Mellitus: A Meta-Analysis

Cited by 4 publications

References 43 publications

Integrating plasma protein-centric multi-omics to identify potential therapeutic targets for pancreatic cancer

Integrating plasma protein-centric multi-omics to identify potential therapeutic targets for pancreatic cancer

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies

Disentangling shared genetic etiologies for kidney function and cardiovascular diseases

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