Archivio Italiano di Urologia e Andrologia 2016; 88, 4270 ORIGINAL PAPER Are erectile functions affected by AB0 blood group? Erdal Benli 1, Abdullah Çırakoğlu 1, Ercan Öğreden 2, Selamettin Demir 3, Yasemin Kaya 4, Mustafa İbas 5, Ali Ayyıldız 6, Ahmet Yüce 1 1 Department of Urology, Ordu University, Faculty of Medicine, Ordu, Turkey; 2 Department of Urology, Giresun University, Faculty of Medicine, Giresun, Turkey; 3 Clinic of Urology, Istanbul Hospital, Van, Turkey; 4 Department of Internal Medicine, Ordu University, Faculty of Medicine, Ordu, Turkey; 5 Intern, Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey; 6 Clinic of Urology, Ankara Training Research Hospital, Ankara, Turkey. Aim: The aim of this study was to investi- gate whether there is a relationship between erectile dysfunction (ED), thought to be a vascular disease, and AB0 blood group. Material and Method: The study included 350 people abiding by the study criteria who applied to our clinic from April 2012-April 2015. The patients were divided into two groups including those with ED (Group 1) and those without (Group 2). Age, blood group, IIEF-5 score and presence of additional diseases were recorded. Erectile functions were analyzed according to blood group. Results: There was no difference between the mean age of 111 patients with ED and that of 239 patients without ED included in the study (p = 0.284). There was no difference between patients in the two groups in terms of smoking, alcohol use, hypertension and diabetes (p > 0.05). Among patients in the ED group, the mean IIEF-5 score according to blood group was 19.8 ± 5.04 in the 0 blood group, 16.5 ± 5.2 in the A blood group, 17.2 ± 5.3 in the B blood group and 13.3 ± 3.02 in the AB blood group. The IIEF-5 scores of individuals in the 0 blood group were significantly high compared to individuals in other blood groups (p = 0.004). Logistic regression analysis found that compared to the 0 blood group, the erectile dys- function risk was 3.9 times greater for the A blood group, 3.5 times greater for the B blood group and 4.7 times greater for the AB blood group (p = 0.001) (Table 3). Conclusion: The risk of erectile dysfunction was significantly increased for individuals in the A, B and AB blood groups compared to individuals in the 0 blood group. KEY WORDS: AB0 blood group; Erectile dysfunction; Vascular disease. Submitted 6 May 2016; Accepted 31 May 2016 Summary No conflict of interest declared. factors such as aging, hypertension, diabetes, smoking, central obesity and dyslipidemia increasing the risk of ath- erosclerotic coronary artery disease (CAD) are also impor- tant risk factors for ED. For both CAD and ED, early indi- cators of the common vascular disease of atherosclerosis may occur in erectile tissue (2, 3). The relationship between AB0 blood groups and some dis- eases was first reported by Alexzender for the first time in 1921 (4). Later studies have reported a close relationship between vascular diseases like coronary artery disease and thrombosis, and also a variety of cancers such as pancre- atic and bladder cancer (5, 6). According with the demon- strated correlation with many vascular diseases, the corre- lation between AB0 blood groups and another vascular disorder such as ED has not been investigated. In this study we aimed to investigate whether there was a corre- lation between AB0 blood groups and erectile dysfunction. MATERIALS AND METHODS The data belonging to 972 patients applying to our clin- ic from April 2012 to April 2015 were retrospectively investigated. The study included 350 patients with age, blood group, IEFF-5 score and presence of additional diseases recorded. Permission was obtained from the local ethics committee of Ordu University (decision no. 2015/1). The exclusion criteria for the study included congestive heart failure, hyperprolactinemia, hypogo- nadism, renal function disorders, peripheral or auto- nomic neuropathy, psychiatric problems and treatment for sexual function disorders. Patients were divided into two groups; those requiring treatment due to lack of or to unsustained erections (ED group) and those with problem-free sexual relations (control group). The erectile functions of patients were determined using the International Index of Erectile Function-5 (IIEF-5). Each question on this from is scored from 1 to 5. If the patient could not fill out the form, help was given by the same person. The total IIEF-5 score is calculated by adding the scores (from 1-5) given to 5 questions. According to total points sexual function was defined as normal (22-25), mild (17-21), moderate (12-16) and severe dysfunction (1-11). DOI: 10.4081/aiua.2016.4.270 INTRODUCTION Erectile dysfunction (ED) is defined as either continuous or repeated lack of erection, or lack of sustained erection, necessary for satisfying sexual relations (1). The penis includes a very rich and specialized vascular system. The complete endothelium furnishing this vascular system plays an important role in erectile tissue function. Disruption of the complete endothelial may cause devel- opment of atherosclerotic vein diseases, in addition to affecting erectile functions. Studies have shown that risk Benli_Stesura Seveso 09/01/17 09:52 Pagina 270 271Archivio Italiano di Urologia e Andrologia 2016; 88, 4 AB0 blood types and erectile dysfunction RESULTS The mean age of all patients included in the study was 62.34 ± 8.51 (41-84) years. The mean age of the 111 patients in the ED group was 63.05 ± 8.5 (41-84) years, while the mean age of patients in the control group with- out ED complaints was 62 ± 8.5 (43-84) years. There was no difference between the groups in terms of age (p = 0.284). Apart from cardiac disease, there was no difference between patients in the ED group and those in the non-ED group in terms of demographic characteristics (Table 1). The distribution of individuals with erectile dysfunction in terms of blood groups is shown in Table 2. The mean IIEF-5 score of patients in the ED group according to blood group was found as 19.8 ± 5.04 for 0 blood group, 16.5 ± 5.2 for A blood group, 17.2 ± 5.3 for B blood group and 13.3 ± 3.02 for AB blood group. The mean IIEF-5 score for individuals with the 0 blood group was identified to be significantly high compared to other blood groups (p = 0.004). The presence of ED was found in 15.7% of patients with 0 blood group, in 41.6% of patients with A blood group, in 39.3% of patients with B blood group and in 46.7% of patients with AB blood group (p < 0.001). Logistic regression analysis showed that compared to the 0 blood group the risk of erectile dysfunction was 3.9 times increased for A blood group, 3.5 times increased for B blood group and 4.7 times increased for AB blood group (p = 0.001) (Table 3). Statistical analysis Descriptive statistics for continuous variables are given as mean, standard deviation, minimum and maximum val- ues, while for categorical variables these are given as number and percentage. To determine whether there was a difference in ED presence for continuous variables, the Student t test was performed. To determine the correla- tion between categorical variables, the chi-square test was used. Additionally to determine the possible risk fac- tors affecting erectile dysfunction, multiple logistic regression analysis was performed. For calculations the level of statistical significance was taken as 5% and cal- culations used the SPSS (ver. 13) statistical package pro- gram. DISCUSSION The results of our study found a relationship between ED and AB0 blood groups and ED was identified to have increased incidence in A, B and AB blood groups com- pared to 0 blood group. The clearly increased ED risk in the AB blood group may be related to the synergic effect caused by the presence of A and B antigens together. The increased risk identified in the study using multivariate analysis shows the ED risk is independent of promoting factors such as alcohol, smoking and hypertension. The penis, with a very rich vein network, is one of the richest organs in terms of endothelium per unit area (7). Healthy endothelium releases material with antifibri- nolytic and anticoagulant properties, as well as strong vasodilatator materials like NO. Disruption of the com- pleteness of the endothelium disrupts these functions and synthesis of vasoconstrictor materials like throm- boxane A2, endotelin, and angiotensin 2 increases. Additionally loss of the permeability and antithrombo- cyte properties of endothelium is proposed to trigger the atherosclerotic process (8). As a result, studies related to atherosclerotic vascular diseases have frequently used measurements of endothelial functions. Diseases that form a risk for vascular disease, like hypertension, hypercholesterolemia, diabetes and obesity, affect the endothelin in the vein walls, by affecting homeostasis function (9). As a result the process beginning with endothelial disruption is reported to show itself in a vari- ety of diseases such as angina, stroke and CAD where tis- sue perfusion is disrupted (9, 10). The degree of endothelial dysfunction is related to the severity of these diseases experienced by the patient (11). Endothelial dysfunction is shown to be an effective factor in the development of ED (12). This effect is thought to be due to effects on the vein elasticity of erectile tissue and on the release of endothelial factors like NO released by endothelium (13, 14). A study by Davignon et al. proposed Table 1. Demographic characteristics of participants in the research. Characteristics ED n (%) P-value (Present/absent) Present Absent Alcohol Present 9 (33.7) 18 (66.7) 0.832 Absent 101 (31.6) 219 (68.4) Smoking Present 38 (33) 77 (67) 0.728 Absent 73 (31.2) 161 (68.8) Diabetes Present 26 (37.7) 43 (62.3) 0.289 Absent 84 (31) 187 (69) Hypertension Present 37 (33.3) 74 (66.7) 0.711 Absent 73 (31.1) 162 (68.9) Cardiac disease Present 29 (43.9) 37 (56.1) 0.27 Absent 82 (73.9) 202 (84.5) Table 2. Distribution of blood groups in ED. Blood group Erectile dysfunction n (%) Present Absent 0 blood group 21 (18.9%) 113 (47.3) A blood group 52 (46.8) 73 (30.5) B blood group 24 (21.6) 37 (15.5) AB blood group 14 (12.6) 16 (6.7) Table 3. Results of logistic regression analysis. Odds ratio (OR) 95.0% C.I. P-value Lower Upper Age 1.009 .979 1.040 0.556 A blood group 3.949 2.143 7.279 0.001 B blood group 3.504 1.712 7.173 0.001 AB blood group 4.742 1.960 11.473 0.001 OR: Odds ratio; CI: Confidence interval. For blood group 0 is the reference category. Benli_Stesura Seveso 09/01/17 09:52 Pagina 271 Archivio Italiano di Urologia e Andrologia 2016; 88, 4 E. Benli, A. Çırakoğlu, E. Öğreden, S. Demir, Y. Kaya, M. İbas, A. Ayyıldız, A. Yüce 272 that one of the earliest indicators of atherosclerosis is changes in NO activity (15). Thus, ED is thought to occur as a part of the systemic vascular disease of atherosclerosis (16). Many studies on this topic have shown a close rela- tionship between ED and vascular diseases. In fact, some studies have proposed ED is the first symptom of systemic vascular disease. Montorsi et al. in a study reported that problems related to ED began 3 years before the occur- rence of coronary artery disease, while Ponholzer et al. reported such problems began 10 years before stroke (17, 18). While explaining the reasons for this, the researchers used the artery diameter hypothesis. According to this hypothesis, as the size of penile arteries (1-2 mm) is small compared to coronary arteries (3-4 mm), the same level of atherosclerotic/endothelial damage causes greater reduc- tion in perfusion in erectile tissue compared to coronary or other veins (19). As a result ED may occur in erectile tissue as the first indicator of systemic atherosclerosis (20, 21). Researchers have proposed that erectile tissue may be a sensitive indicator of systemic atherosclerotic diseases (7). The reason for the relationship between AB0 blood groups and ED identified in our study may be related to endothelial dysfunction and related atherosclerosis occur- ring in erectile tissue. Many studies supporting this hypothesis have shown a relationship between athero- sclerotic vascular diseases and AB0 blood groups (1). Atherosclerotic vascular diseases like myocardial infarct, peripheral vascular diseases, intermittent claudication, and venous thromboembolism are reported to be encoun- tered more frequently in the non-0 blood groups com- pared to the 0 blood group (22, 23). A study by Carpenggiani et al. investigated the blood groups of 4901 patients undergoing coronary angiography due to athero- sclerotic CAD and reported that atherosclerotic coronary disease was most frequently observed in non-0 blood groups (24). This conclusion may explain our results. Probably blood groups cause atherosclerotic results or endothelial dysfunction leading to development of ED. The reason for the relationship between AB0 blood groups and atherosclerotic vascular diseases is not fully known. The genetic nature of the AB0 blood groups may affect this. There are many hypotheses to explain this sit- uation. One of these is the ATP-binding cassette 2 (ABCA2) gene known to be important for cholesterol balance and carried in the 9q34 locus of chromosome 9 together with AB0 blood groups (25, 26). The study by Carpeggiani et al. identified a significant relationship between non-0 blood group and hypercholesterolemia and family history (24). In human and animal models, hypercholesterolemia is shown to disrupt smooth muscle relaxation linked to endothelium, enzyme activity of endothelial nitric oxide synthesis (eNOS) and penile angiogenesis resulting in ED (16, 27). Another hypothe- sis is related to adhesion molecules such as sICAM-1 (high soluble intercellular adhesion molecule-1), sP- selectin (soluble P-selectin) and sE-selectin (soluble E- selectin) which affect AB0 blood groups and are thought to cause endothelial disruption (28). Another opinion gaining great interest is related to blood groups affecting von Willebrand factor (vWF) and factor 8 levels causing development of atherosclerosis (29). These factors, known as adhesion molecules, are reported to be effective on thrombocyte leukocyte interaction, adhesion of thrombocytes to veins, migration of leukocytes into veins and development of atheroma plaque; in short on the development of atherosclerosis (30, 31). Studies have identified higher vWF and F8 levels in individuals with A and B blood groups compared to 0 blood group (32, 33). The study by Sarode et al. reported that A and B blood groups were effective on adhesive activity of vWF (34). Again a study by Ray et al. on acute coronary syndrome and a study by Convay et al. on thromboemboli and stroke diseases reported a close relationship between AB0 blood group and vWF (35, 36). In short there are many studies in the literature showing the close relationship between AB0 blood groups and atherosclerotic vascular diseases (37). In fact a study by Kaya et al. reported that AB0 blood groups may be relat- ed to the complications of atherosclerosis, in addition to the development of atherosclerosis (38). In our study, A, B and AB blood groups were found to be related to the risk of a person experiencing erectile dys- function. As mentioned in many studies above, due to the relationship shown between vascular diseases and AB0 blood groups, the relationship with ED thought to be a vascular disease is not surprising. We consider that this effect progresses through endothelial dysfunction and atherosclerotic processes. We consider that endothe- lial damage affects synthesis of a variety of materials like NO known to play an important role in erections, dis- rupts the effect of endothelium on vascular tonus, nar- rows the venous lumens due to atherosclerosis and final- ly affects blood flow to erectile tissue. There are some limitations to this study. These include its retrospective nature, reflecting results from a single center and that laboratory results from patients including lipid profile, serum F8 and vWF level were not examined. CONCLUSION This study found a close relationship between A, B and AB blood groups and ED. We believe this correlation is due to effect of the complicated process resulting in endothelial dysfunction, similar to the correlation previously reported for blood groups and atherosclerotic events. In spite of the limitations of the study, we believe this study is very impor- tant in being the first study to show the relationship between AB0 blood groups and ED. 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Correspondence Erdal Benli, MD (Corresponding Author) drerdalbenli@gmail.com Abdullah Çırakoğlu, MD dr_cirakoglu@yahoo.com Ahmet Yüce, MD ahmetyuce7@gmail.com Department of Urology, Ordu University, Faculty of Medicine, Ordu, Turkey Ercan Öğreden, MD 9isik061@mynet.com Department of Urology, Giresun University, Faculty of Medicine, Giresun, Turkey Selamettin Demir, MD drselami1978@hotmail.com Clinic of Urology, Istanbul Hospital, Van, Turkey Mustafa İbas, MD ibasmustafa91@hotmail.com Intern, Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey Ali Ayyıldız, MD urology52@gmail.com Clinic of Urology, Ankara Training Research Hospital, Ankara, Turkey Benli_Stesura Seveso 09/01/17 09:52 Pagina 273