Uremic Pruritus Is Not Associated with Endocannabinoid Receptor 1 Gene Polymorphisms

Uremic pruritus (UP) is a frequent and bothersome symptom in hemodialysis patients. Its etiology is not fully understood and that is why there is no specific treatment. The endocannabinoid system plays a role in many pathological conditions. There is reliable evidence on the association between cannabinoid system and pruritus. In our study, we aimed to evaluate whether genetic variations in the endocannabinoid receptor 1 (CNR1) gene can affect UP. The rs12720071, rs806368, rs1049353, rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 159 hemodialysis patients and 150 healthy controls using two multiplex polymerase chain reactions and the minisequencing technique. No statistically significant relationship was found in any of the evaluated genotypes between patients with and without UP, even after excluding patients with diabetes and dyslipidemia. There were no differences between patients with UP and the control group. However, in the group of all HD patients, a significantly higher incidence of GA genotype and lower incidence in GG genotype in the polymorphism rs806381s were revealed versus the control group (p = 0.04). It seems that polymorphisms of the CNR1 gene are not associated with uremic pruritus.

[1]  L. Iversen Endocannabinoids , 2018, Oxford Scholarship Online.

[2]  J. P. Teixeira,et al.  Pruritus in Kidney Disease. , 2015, Seminars in nephrology.

[3]  A. Milewicz,et al.  Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome , 2015, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[4]  S. Kinsey,et al.  The endocannabinoid system modulates stress, emotionality, and inflammation , 2014, Brain, Behavior, and Immunity.

[5]  A. Milewicz,et al.  Cannabinoid Receptor 1 Gene Polymorphisms and Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome and in Healthy Controls , 2014, International journal of endocrinology.

[6]  A. Milewicz,et al.  ADRB3 and PPARγ2 gene polymorphisms and their association with cardiovascular disease risk in postmenopausal women , 2013, Climacteric : the journal of the International Menopause Society.

[7]  R. Ji,et al.  New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? , 2013, Pflügers Archiv - European Journal of Physiology.

[8]  W. Marsden I and J , 2012 .

[9]  A. Milewicz,et al.  Endocannabinoid type 1 receptor gene (CNR1) polymorphisms (rs806381, rs10485170, rs6454674, rs2023239) and cardiovascular risk factors in postmenopausal women , 2011, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[10]  Stephen P. H. Alexander,et al.  International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2 , 2010, Pharmacological Reviews.

[11]  S. Murray,et al.  Biomarkers of Endocannabinoid System Activation in Severe Obesity , 2010, PloS one.

[12]  J. Szepietowski,et al.  Cannabinoid system in the skin – a possible target for future therapies in dermatology , 2009, Experimental dermatology.

[13]  A. Floreani,et al.  Hepatic expression of endocannabinoid receptors and their novel polymorphisms in primary biliary cirrhosis , 2009, Journal of Gastroenterology.

[14]  T. Carr,et al.  Endocannabinoids, metabolic regulation, and the role of diet. , 2008, Nutrition research.

[15]  T. Hansen,et al.  Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations. , 2008, Human molecular genetics.

[16]  Laurent Misery,et al.  The epidermis: a sensory tissue. , 2008, European journal of dermatology : EJD.

[17]  Yan Sun,et al.  Cannabinoids: A New Group of Agonists of PPARs , 2007, PPAR research.

[18]  T. Luger,et al.  [Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus]. , 2006, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[19]  Michael Koblish,et al.  Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain. , 2005, European journal of pharmacology.

[20]  T. Luger,et al.  Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. , 2005, Journal of dermatological science.

[21]  J. Szepietowski,et al.  Emollients With Endocannabinoids in the Treatment of Uremic Pruritus: Discussion of the Therapeutic Options , 2005, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy.

[22]  C. Konrad,et al.  [Cannabinoids--signal transduction and mode of action]. , 2005, Schmerz.

[23]  Archiv Pharmakologie Pflügers Archiv European Journal of Physiology , 2005, Klinische Wochenschrift.

[24]  J. Szepietowski,et al.  Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. , 2005, Acta dermatovenerologica Croatica : ADC.

[25]  C. Konrad,et al.  Cannabinoide—Signaltransduktion und Wirkung , 2005, Der Schmerz.

[26]  J. Szepietowski,et al.  Uremic pruritus: still an important clinical problem. , 2004, Journal of American Academy of Dermatology.

[27]  R. Schwartz,et al.  Uraemic xerosis. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  G. Yosipovitch,et al.  Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease. , 2003, Journal of the American Academy of Dermatology.

[29]  J. Szepietowski,et al.  Uremic Pruritus: A Clinical Study of Maintenance Hemodialysis Patients , 2002, The Journal of dermatology.

[30]  E. Schiff,et al.  Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease , 2002, American Journal of Gastroenterology.

[31]  A. Rice,et al.  The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain , 1998, Pain.

[32]  A. Buriani,et al.  Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. , 1995, Proceedings of the National Academy of Sciences of the United States of America.