Lack of Association between C385A Functional Polymorphism of the Fatty Acid Amide Hydrolase Gene and Polycystic Ovary Syndrome

V. K. Grolmusz; B. Stenczer; T. Fekete; G. Szendei; A. Patócs; K. Rácz; P. Reismann

doi:10.1055/s-0033-1337941

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2013; 121(06): 338-342
DOI: 10.1055/s-0033-1337941

Article

Lack of Association between C385A Functional Polymorphism of the Fatty Acid Amide Hydrolase Gene and Polycystic Ovary Syndrome

Authors

V. K. Grolmusz

³2nd Department of Medicine, Semmelweis University, Budapest, Hungary
B. Stenczer

²1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
T. Fekete

²1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
G. Szendei

²1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
A. Patócs

³2nd Department of Medicine, Semmelweis University, Budapest, Hungary
K. Rácz

³2nd Department of Medicine, Semmelweis University, Budapest, Hungary
P. Reismann

¹Semmelweis Univ., Budapest, Hungary

Abstract

Introduction:

The endocannabinoid system contributes to the regulation of appetite, food intake and energy balance. Fatty acid amide hydrolase is responsible for degradating anandamide, a key messenger of the endocannabinoid system. C385A is a common, functionally active genetic polymorphism of the gene encoding fatty acid amide hydrolase and has been associated with overweight and obesity. Our aim was to establish whether single nucleotide polymorphism C385A has an association with polycystic ovary syndrome or its clinical features.

Materials and Methods:

A monocentric pilot study was performed on 63 patients with polycystic ovary syndrome and 67 healthy control subjects. Anthropometric parameters and laboratory data were acquired from subjects. The alleles of the polymorphism were detected using polymerase chain reaction and subsequent cleavage by Eco130I (StyI) restriction endonuclease verified by direct DNA sequencing.

Results:

No difference was found in minor allele frequency between patient and control groups. Those patients, carrying the C385A polymorphism were associated with higher free thyroxine hormone levels. In the control group, carriers of the polymorphism had significantly lower insulin levels.

Discussion and Conclusions:

Our data indicate that the C385A polymorphism of the fatty acid amide hydrolase gene is not a genetic susceptibility factor for the development of polycystic ovary syndrome. However, the polymorphism might have a role in influencing the synthesis or metabolism of different hormones including thyroxin and insulin.

Key words

FAAH - PCOS - endocannabinoid system - SNP

Full Text

References

References
1 Azziz R, Woods KS, Reyna R et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745-2749
2 Asuncion M, Calvo RM, San Millan JL et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000; 85: 2434-2438
3 Tehrani FR, Simbar M, Tohidi M et al. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Reprod Biol Endocrinol 2011; 9: 39
4 Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-191
5 Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR. (ed.). Polycystic ovary syndrome. Boston: Blackwell; 1992: 337-384
6 Rotterdam, ESHRE-ASRM-sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
7 Azziz R, Carmina E, Dewailly D et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456-488
8 Azziz R, Carmina E, Dewailly D et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91: 4237-4245
9 Rachon D. Differential diagnosis of hyperandrogenism in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2012; 120: 205-209
10 Vrbikova J, Hainer V. Obesity and polycystic ovary syndrome. Obes Facts 2009; 2: 26-35
11 Essah PA, Nestler JE. The metabolic syndrome in polycystic ovary syndrome. J Endocrinol Invest 2006; 29: 270-280
12 Moran LJ, Misso ML, Wild RA et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16: 347-363
13 DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83: 1454-1460
14 Goodarzi MO, Dumesic DA, Chazenbalk G et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011; 7: 219-231
15 Mak W, Dokras A. Polycystic ovarian syndrome and the risk of cardiovascular disease and thrombosis. Semin Thromb Hemost 2009; 35: 613-620
16 Carmina E. Cardiovascular risk and events in polycystic ovary syndrome. Climacteric 2009; 12 (Suppl. 01) 22-25
17 Martinez-Bermejo E, Luque-Ramirez M, Escobar-Morreale HF. Obesity and the polycystic ovary syndrome. Minerva Endocrinol 2007; 32: 129-140
18 Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol 2010; 160: 480-498
19 Bellocchio L, Cervino C, Pasquali R et al. The endocannabinoid system and energy metabolism. J Neuroendocrinol 2008; 20: 850-857
20 Pagotto U, Pasquali R. Endocannabinoids and energy metabolism. J Endocrinol Invest 2006; 29 (3 Suppl) 66-76
21 Bari M, Battista N, Fezza F et al. New insights into endocannabinoid degradation and its therapeutic potential. Mini Rev Med Chem 2006; 6: 257-268
22 Fezza F, De Simone C, Amadio D et al. Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system. Subcell Biochem 2008; 49: 101-132
23 Camilleri M, Carlson P, McKinzie S et al. Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am J Physiol Gastrointest Liver Physiol 2008; 294: G13-G19
24 Chiang KP, Gerber AL, Sipe JC et al. Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet 2004; 13: 2113-2119
25 Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG 2006; 113: 1148-1159
26 Rossato M, Ion Popa F, Ferigo M et al. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005; 90: 984-991
27 Maccarrone M. Endocannabinoids: friends and foes of reproduction. Prog Lipid Res 2009; 48: 344-354
28 Maccarrone M, Valensise H, Bari M et al. Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage. Lancet 2000; 355: 1326-1329
29 Maccarrone M, Bisogno T, Valensise H et al. Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. Mol Hum Reprod 2002; 8: 188-195
30 Sipe JC, Waalen J, Gerber A et al. Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 2005; 29: 755-759
31 Sipe JC, Scott TM, Murray S et al. Biomarkers of endocannabinoid system activation in severe obesity. PloS One 2010; 5: e8792
32 Jensen DP, Andreasen CH, Andersen MK et al. The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites. J Mol Med (Berl) 2007; 85: 445-449
33 Papazoglou D, Panagopoulos I, Papanas N et al. The fatty acid amide hydrolase (FAAH) Pro129Thr polymorphism is not associated with severe obesity in Greek subjects. Horm Metab Res 2008; 40: 907-910
34 de Luis DA, Sagrado MG, Aller R et al. C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance in patients with diabetes mellitus type 2. Diabetes Res Clin Pract 2010; 88: 76-80
35 de Luis DA, Gonzalez Sagrado M, Aller R et al. Relation of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) with obesity and insulin resistance. Nutr Hosp 2010; 25: 993-998
36 Sarzani R, Bordicchia M, Salvi F et al. A human fatty acid amide hydrolase (FAAH) functional gene variant is associated with lower blood pressure in young males. Am J Hypertens 2008; 21: 960-963
37 Aberle J, Fedderwitz I, Klages N et al. Genetic variation in two proteins of the endocannabinoid system and their influence on body mass index and metabolism under low fat diet. Horm Metab Res 2007; 39: 395-397
38 de Luis DA, Gonzalez Sagrado M, Aller R et al. Effects of C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase on weight loss after a hypocaloric diet. Metabolism 2011; 60: 730-734
39 Zeng J, Li J, Huang G. 385 C/A polymorphism of the fatty acid amide hydrolase gene is associated with metabolic syndrome in the Chinese Han population. Arch Med Sci 2011; 7: 423-427
40 de Luis DA, Aller R, Izaola O et al. Relationship among metabolic syndrome, C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance. J Diabetes Complications 2012; 26: 328-332