Abstract
ABO blood group antigens have been associated with various cardiovascular and inflammatory diseases; however, their relationship with peripheral nervous system disorders remains unclear. The primary aim of this study was to investigate the association between ABO and Rh blood groups and diabetic polyneuropathy in a large hospital-based population; the secondary aim was to evaluate the potential association of these blood groups with nondiabetic polyneuropathy. In this retrospective study, records of individuals with available ABO and Rh blood group data between January 2014 and December 2025 were reviewed. Participants were categorized into 3 groups: controls without peripheral neuropathy, patients with polyneuropathy without diabetes mellitus (nondiabetic polyneuropathy), and patients with diabetic polyneuropathy. A total of 21,427 individuals were included after applying the eligibility criteria and data cleaning. Blood group distributions were compared among the groups, and multinomial logistic regression analysis was performed to evaluate associations with disease status after adjustment for age, sex, and Rh factor. The study included 18,150 controls, 1697 patients with nondiabetic polyneuropathy, and 1580 patients with diabetic polyneuropathy. No significant differences were observed among the 3 groups in terms of ABO blood group distribution or Rh factor. After adjustment for age, sex, and Rh factor, no significant association was found between ABO blood groups and nondiabetic polyneuropathy. In contrast, blood group A was associated with higher odds of diabetic polyneuropathy compared with blood group O (adjusted OR 1.171, 95% CI 1.031–1.330; P = .015). The Rh factor was not significantly associated with either condition after adjustment for the available covariates. Blood group A was associated with diabetic polyneuropathy, whereas no significant association was found between ABO blood groups and nondiabetic polyneuropathy. Given the etiological heterogeneity of nondiabetic polyneuropathy and the retrospective nature of the study, these findings should be interpreted with caution and further evaluated in prospective studies with appropriate control groups and etiologically more homogeneous patient populations.
Keywords: ABO blood group, blood group distribution, diabetic polyneuropathy, epidemiology, peripheral neuropathy, Rh factor
1. Introduction
The ABO blood group system is one of the most well-known genetic polymorphisms in humans and is expressed not only on erythrocytes but also on endothelial cells, platelets, and various epithelial tissues. Therefore, ABO blood group antigens are considered to play a role not only in transfusion medicine but also in the pathophysiology of various diseases.[1–6] Recent studies have suggested an association between ABO blood groups and cardiovascular diseases, thromboembolic events, and inflammatory processes.[2–5] This relationship is thought to be mediated by the effects of ABO antigens on endothelial function, the coagulation system, and the inflammatory response.[2–6]
Although studies investigating the association between ABO blood groups and various diseases have increased in recent years, research evaluating their relationship with neurological disorders remains limited. It has been reported that ABO blood group distribution may differ in certain neurological conditions, such as migraine.[7] However, studies examining the relationship between peripheral nervous system disorders and the ABO blood group system are scarce.[8,9] Therefore, investigating the potential association between peripheral neuropathy and ABO/Rh blood group distribution may contribute to the existing literature.
Polyneuropathy is a heterogeneous group of disorders characterized by widespread involvement of peripheral nerves and may develop due to various etiological factors.[10,11] Diabetic polyneuropathy, on the other hand, is one of the most common chronic complications of diabetes and leads to structural and functional changes in peripheral nerves.[12,13] It is well established that mechanisms such as hyperglycemia-induced metabolic changes, oxidative stress, inflammation, and microvascular damage play important roles in the pathogenesis of diabetic polyneuropathy.[13–15]
Considering that the ABO blood group system is associated with vascular and inflammatory mechanisms, it may be hypothesized that blood groups could have an indirect role in the development of diabetic neuropathy.[8,9] However, there is insufficient evidence on this topic. Therefore, this study aimed to investigate the association between ABO and Rh blood groups and polyneuropathy and diabetic polyneuropathy in a large hospital-based population.
2. Material and methods
2.1. Study design
This study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.[16] This retrospective observational study was conducted using the electronic medical record system of our hospital. Records of individuals with available ABO and Rh blood group data between January 2014 and December 2025 were reviewed. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Ankara Atatürk Sanatoryum Training and Research Hospital (2024 BCEK/532). Demographic variables, including age and sex, as well as ABO and Rh blood group data, were extracted for analysis.
2.2. Study population
Polyneuropathy and diabetic polyneuropathy were retrospectively identified using ICD-10 diagnostic codes recorded in the hospital information system and assigned by neurologists during routine clinical practice. Diabetic polyneuropathy was defined as the presence of documented diagnoses of both diabetes mellitus and diabetic peripheral neuropathy. Eligible individuals with available ABO and Rh blood group data were classified into 3 groups based on their recorded diagnoses: controls, including individuals without documented polyneuropathy or diabetic polyneuropathy; patients with polyneuropathy; and patients with diabetic polyneuropathy.
Individuals with recorded ABO and Rh blood group information in the hospital database were eligible for inclusion. Prior to statistical analysis, the dataset was assessed for data consistency, and records with missing or erroneous blood group coding were excluded.
2.3. Blood group classification
Blood groups were classified according to the ABO system as A, B, AB, and O. The Rh factor was categorized as positive (Rh+) or negative (Rh−). Blood group data were obtained from laboratory records within the hospital information system.
2.4. Outcomes
The primary objective of this study was to investigate whether ABO and Rh blood groups are independently associated with polyneuropathy and diabetic polyneuropathy in a large hospital-based population.
The secondary objectives were:
to compare the distribution of ABO and Rh blood groups among the control, polyneuropathy, and diabetic polyneuropathy groups;
to evaluate the effects of age, sex, ABO blood group, and Rh factor on disease status using multinomial logistic regression analysis; and
to quantify the association between individual ABO blood groups and disease status by calculating adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs), using blood group O as the reference category.
2.5. Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0 (IBM, USA). Continuous variables were tested for normality using the Kolmogorov-Smirnov test. As the data were not normally distributed, continuous variables are presented as median (interquartile range, IQR 25–75) and were compared using the Kruskal–Wallis test. Categorical variables are expressed as numbers and percentages and were compared using the Pearson chi-square test.
To determine whether ABO blood groups were independently associated with polyneuropathy and diabetic polyneuropathy, a multinomial logistic regression analysis was performed using the control group as the reference category. Blood group O was selected as the reference category for ABO blood groups. Age was entered as a covariate, whereas sex, Rh factor, and ABO blood group were included as categorical variables in the model. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. A two-sided P-value of < .05 was considered statistically significant.
3. Results
A total of 21,427 participants were included in the study. The baseline demographic characteristics and distribution of ABO/Rh blood groups are presented in Table 1. Comparisons among the control, polyneuropathy, and diabetic polyneuropathy groups are summarized in Table 2. Both the polyneuropathy and diabetic polyneuropathy groups were significantly older than the control group (P < .001 for both comparisons). In addition, the proportion of male participants differed significantly among the 3 groups (P < .001). However, the overall distribution of ABO blood groups did not differ significantly among the control, polyneuropathy, and diabetic polyneuropathy groups (P = .155). Likewise, no significant difference was observed in Rh factor distribution (P = .676).
Table 1.
Baseline demographic characteristics and ABO/Rh blood group distribution of the study population.
| Sex, n (%) | |
| Female | 13186 (61.5%) |
| Male | 8241 (38.5%) |
| Age, median (IQR, 25–75) | 54 (36–69) |
| Blood Group, n (%) | |
| A | 9179 (42.8%) |
| B | 3609 (16.8%) |
| O | 6893 (32.2%) |
| AB | 1746 (8.1%) |
| Rh Factor, n (%) | |
| Rh (+) | 19019 (88.8%) |
| Rh (−) | 2408 (11.2%) |
| Groups, n (%) | |
| Control | 18150 (84.7%) |
| nonDiabetic Polyneuropathy | 1697 (7.9%) |
| Diabetic Polyneuropathy | 1580 (7.4%) |
Rh = Rhesus factor.
Table 2.
Comparison of demographic characteristics and ABO/Rh blood group distributions among the control, nondiabetic polyneuropathy, and diabetic polyneuropathy groups.
| Control (n = 18.150) | nonDiabetic Polyneuropathy (n = 1.697) | Diabetic Polyneuropathy (n = 1.580) | P value | |
|---|---|---|---|---|
| Male sex, n (%) | 6720 (37%) | 888 (52.3%) | 633 (40.1%) | <.001 |
| Age, median (IQR, 25–75) | 48 (33–66) | 71 (62–79) | 71 (62–78) | <.001 |
| Blood Group, n (%) | .155 | |||
| A | 7737 (42.6%) | 721 (42.5%) | 721 (45.6%) | |
| B | 3050 (16.8%) | 288 (17%) | 271 (17.2%) | |
| O | 5893 (32.5%) | 543 (32%) | 457 (28.9%) | |
| AB | 1470 (8.1%) | 145 (8.5%) | 131 (8.3%) | |
| Rh Factor, n (%) | .676 | |||
| Rh (+) | 16103 (88.7%) | 1517 (89.4%) | 1399 (88.5%) | |
| Rh (−) | 2047 (11.3%) | 180 (10.6%) | 181 (11.5%) |
Rh = Rhesus factor.
The results of the multinomial logistic regression analysis, adjusted for age, sex, and Rh factor, are presented in Table 3. Increasing age was independently associated with both polyneuropathy and diabetic polyneuropathy (both P < .001). Male sex was independently associated with polyneuropathy (OR 1.839, 95% CI 1.655–2.042, P < .001), whereas its association with diabetic polyneuropathy did not reach statistical significance (OR 1.115, 95% CI 0.999–1.245, P = .052).
Table 3.
Multinomial logistic regression analysis of factors associated with nondiabetic polyneuropathy and diabetic polyneuropathy.
| Variable | nonDiabetic Polyneuropathy (vs Control) OR (CI) |
P | Diabetic polyneuropathy (vs Control) OR (CI) |
P |
|---|---|---|---|---|
| Age | 1.067 (1.063–1.070) | <.001 | 1.068 (1.064–1.072) | <.001 |
| Rh (+/-) | 0.953 (0.804–1.129) | .574 | 1.043 (0.880–1.235) | .629 |
| Blood group A (reference: blood group O) | 0.972 (0.860–1.099) | .652 | 1.171 (1.031–1.330) | .015 |
| Blood group B (reference: blood group O) | 1.009 (0.862–1.181) | .908 | 1.148 (0.974–1.352) | .099 |
| Blood group AB (reference: blood group O) | 1.088 (0.889–1.332) | .412 | 1.186 (0.959–1.465) | .115 |
| Male sex (reference: female) | 1.839 (1.655–2.042) | <.001 | 1.115 (0.999–1.245) | .052 |
CI = confidence interval, OR = odds ratio, Rh = Rhesus factor.
After adjustment for potential confounders, no significant association was found between ABO blood groups and polyneuropathy. In contrast, blood group A was independently associated with diabetic polyneuropathy, with individuals carrying blood group A having higher odds of diabetic polyneuropathy than those with blood group O (OR 1.171, 95% CI 1.031–1.330, P = .015). Blood groups B and AB, as well as Rh factor, were not independently associated with diabetic polyneuropathy.
4. Discussion
In the present study, which investigated the relationship between ABO and Rh blood groups and peripheral neuropathy in a large hospital-based population, 2 major findings were obtained. First, although the overall distribution of ABO blood groups did not differ significantly among the control, polyneuropathy, and diabetic polyneuropathy groups, multinomial logistic regression analysis demonstrated that blood group A was independently associated with diabetic polyneuropathy after adjustment for age, sex, and Rh factor. Second, no independent association was observed between ABO blood groups and polyneuropathy overall, and Rh factor was not associated with either polyneuropathy or diabetic polyneuropathy. These findings suggest that blood group A may be associated with susceptibility to diabetic polyneuropathy rather than polyneuropathy in general.
ABO blood group antigens are expressed not only on erythrocytes but also on vascular endothelial cells, platelets, epithelial tissues, and neurons, suggesting that their biological effects extend beyond transfusion medicine. Previous studies have demonstrated that ABO blood groups are associated with endothelial function, inflammatory pathways, and coagulation factors, particularly von Willebrand factor and factor VIII levels, which differ between O and non-O blood groups.[1,3–5,17] These biological differences have been implicated in the pathogenesis of several vascular and metabolic disorders and may influence tissue susceptibility to chronic microvascular injury. Because diabetic polyneuropathy develops through a combination of microvascular dysfunction, chronic inflammation, oxidative stress, and metabolic abnormalities, it is biologically plausible that ABO blood group antigens could indirectly contribute to peripheral nerve damage.[9,17,18] Nevertheless, the exact mechanisms linking ABO blood groups with peripheral neuropathy remain unclear, and current evidence is insufficient to establish a causal relationship. Therefore, any observed association should be interpreted cautiously until supported by further mechanistic and prospective studies.
The findings of previous studies investigating the association between ABO blood groups and diabetes and its complications have been inconsistent. Mandal et al reported no statistically significant association between ABO blood groups and type 2 diabetes mellitus; however, when blood group O was used as the reference category, individuals with blood groups A, B, and particularly AB showed a relatively higher risk of developing diabetes. In the same study, although no significant association was observed between ABO blood groups and diabetic neuropathy, nephropathy, or retinopathy, individuals with blood groups A and AB appeared to have a lower risk of developing neuropathy than those with blood group O.[8] In contrast, another prospective cohort study demonstrated that blood group O was associated with a lower risk of type 2 diabetes, whereas blood groups A, B, and AB were associated with an increased risk.[19] However, several other studies failed to demonstrate a significant relationship between ABO blood groups and diabetes.[20] When our findings are interpreted in the context of the existing literature, they suggest that ABO blood groups are not associated with polyneuropathy in general but may have a limited and disease-specific role in the development of diabetic polyneuropathy. Although no independent association was identified between ABO blood groups and overall polyneuropathy, blood group A remained independently associated with diabetic polyneuropathy after adjustment for age, sex, and Rh factor (adjusted OR 1.17, 95% CI 1.03–1.33, P = .015). In contrast, the Rh factor was not independently associated with either polyneuropathy or diabetic polyneuropathy. These findings suggest that ABO blood groups are unlikely to be a primary determinant of peripheral nerve injury but may contribute to the development of diabetic neuropathy through interactions with diabetes-related microvascular and inflammatory mechanisms.[9,17,18] Nevertheless, because only a limited number of studies have specifically evaluated the association between ABO blood groups and diabetic neuropathy, direct comparison of our findings with previous reports remains difficult. The discrepancies among published studies may be explained by differences in genetic background, ethnicity, and environmental factors across study populations.[18] In addition, variations in study design, sample size, and statistical methodology may also have contributed to the observed heterogeneity.
5. Limitations
This study has several limitations. First, its retrospective and single-center design may have introduced selection bias and limited the generalizability of the findings. Second, the diagnoses were based on electronic medical records, and detailed clinical information, including disease severity, duration of diabetes, glycemic control, electrophysiological findings, and treatment history, was not available for analysis. Third, although age and sex were adjusted for in the multivariable analysis, other potential confounding factors such as comorbidities and metabolic parameters could not be evaluated because of the retrospective design.
6. Conclusions
Polyneuropathy and diabetic polyneuropathy are common neurological disorders that contribute substantially to morbidity and impaired quality of life. In the present study, ABO blood groups were not independently associated with polyneuropathy overall. However, after adjustment for age, sex, and Rh factor, individuals with blood group A had a significantly higher likelihood of diabetic polyneuropathy than those with blood group O. Although the observed association was modest, these findings suggest that blood group A may be associated with susceptibility to diabetic polyneuropathy rather than polyneuropathy in general. Further prospective multicenter studies incorporating detailed clinical and metabolic data are warranted to confirm these findings and to clarify the underlying biological mechanisms.
Author contributions
Conceptualization: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Data curation: Hatice Karaer Ünaldı, Volkan Savıcı, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Formal analysis: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Funding acquisition: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Investigation: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Methodology: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Project administration: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Resources: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Beyza Betül Bilgehan.
Software: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Supervision: Hatice Karaer Ünaldı, Emine Emektar, Osman Korucu.
Validation: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Visualization: Hatice Karaer Ünaldı, Volkan Savıcı, Emine Emektar, Osman Korucu, Sinem Fidan Buçin, Melike Bilir, Burcu Karabulut, Ömer Akbudak, Beyza Betül Bilgehan.
Writing – original draft: Hatice Karaer Ünaldı, Volkan Savıcı, Osman Korucu.
Writing – review & editing: Hatice Karaer Ünaldı, Emine Emektar, Osman Korucu.
Abbreviations:
- CI
- confidence interval
- OR
- odds ratio
- Rh
- rhesus factor
The authors have no funding and conflicts of interest to declare.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.;The data that support the findings of this study are available from a third party, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are available from the authors upon reasonable request and with permission of the third party.
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Ankara Atatürk Sanatoryum Training and Research Hospital (approval number: [2024 BCEK/532], approval date: [08.04.2026]).
How to cite this article: Karaer Ünaldı H, Savıcı V, Emektar E, Korucu O, Fidan Buçin S, Bilir M, Karabulut B, Akbudak Ö, Bilgehan BB. Association of ABO and Rh blood groups with diabetic polyneuropathy: A retrospective cross-sectional study. Medicine 2026;105:43(e51286).
Contributor Information
Volkan Savıcı, Email: volkansavici@gmail.com.
Emine Emektar, Email: emineakinci@yahoo.com.
Osman Korucu, Email: osmankorucu@yahoo.com.
Sinem Fidan Buçin, Email: drsinemfidan@gmail.com.
Melike Bilir, Email: blrmelike95@gmail.com.
Burcu Karabulut, Email: bb.karabulut5@gmail.com.
Ömer Akbudak, Email: omerakbdk@hotmail.com.
Beyza Betül Bilgehan, Email: beyzabilden@gmail.com.
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