Studying the genotype of Aryl Hydrocarbon Receptor-Interacting Protein (AIP) Gene (rs641081C>A) in Iraqi Samples with Acromegaly Pituitary Adenoma
Keywords:Acromegaly, Aryl hydrocarbon receptor-interacting protein, Gene polymorphism, Pituitary adenoma
Pituitary adenomas are the anterior pituitary tumors. Patients with an Aryl Hydrocarbon Receptor-Interacting Protein (AIP) mutation (AIP- mut) tend to have more aggressive tumors occurring at a younger age. Single nucleotide polymorphisms (SNPs) in many studies have been related to metabolic comorbidities in the general population. Study aims investigated the role of AIP gene SNPs with susceptibility to acromegaly pituitary- adenoma, with levels of LH, FSH, TSH, Testosterone, IGF1,GH, FT4 , Prolactin hormones and blood sugar levels. The study was conducted on a group of acromegaly patients, including 50 patients) both Genders( with hyperplasia of the ends, and apparently healthy control group. Genotyping of AIP gene SNP (rs641081C >A) was indicated significant differences in frequency percentage between the study groups. The frequency of heterozygous CA genotype was significantly (p<0.01) higher in the patients' group when compared with control. The Means of IGF1, GH, prolactin, testosterone, and FBS were significantly higher in patients at first treatment than that in control. While, the means of IGF1, GH, prolactin, and testosterone increased significantly in patients at last treatment than control. Patients mean level of TSH decreased significantly at last treatment. No significant differences (P ≥ 0.05) were detected between study groups in all other values. The Means of IGF1, GH, and prolactin at first and last treatment were significantly decreased, while LH was significantly increased at last treatment. In patients with heterozygous mutant and wild genotype, means of IGF1, GH, and prolactin decreased significantly at last treatment compared to first treatment. In this study heterozygous rs641081C>A showed a risk factor for susceptibility of acromegaly. Also, serum IGF1, GH, prolactin, were affected by the SNP of AIP gene within carriers of genotypes of rs641081C>A. IGF1, prolactin and GH decreased significantly at last treatment compared to first treatment.
Published Online First 20/5/2022
Russ S, Shafiq I. Pituitary Adenoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Feb 4. PMID: 32119338 , Bookshelf ID: NBK554451
Makri A, Lodish M. Gigantism and Acromegaly. In Pituitary Disorders of Childhood. Humana Press, Cham. 2019: 121-139 p.
3. Al-Yasseri BJ, Rahmah AM, Al-Saffar NS. Acromegaly in Iraq: Brief look on epidemiology, comorbidities and management. J Contemp Med Sci 2019Jun28;5(3):136-139, doi.org/10.22317/jcms.06201903
Chris Yedinak1, Karen J. Pulaski-Liebert, Daphne T. Adelman , Jessica Williams. Acromegaly: current therapies benefits and burdens. Clin. Pract. (2018) 15(2), 499-511.
Daly AF, Rostomyan L, Betea D, Bonneville JF, Villa C, Pellegata NS, et al.,. AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients. Endocrine Connections J., 2019 Apr 1; 8(4): 367-77. DOI: 10.1530/EC-19-0004
Rostomyan L, Daly AF, Petrossians P, Nachev E, Lila AR, Lecoq AL, Lecumberri B, Trivellin G, Salvatori R, Moraitis AG, Holdaway I. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Connect. 2015 Oct 22(5): 745-57. DOI: 10.1530/ERC-15-0320
Lenders NF, McCormack AI, Ho KK. Management of endocrine diseases: does gender matter in the management of acromegaly. Eur J Endocrinal. 2020 May 1; 182(5): R67-82. DOI: 10.1530/EJE-19-1023
Colao A, Amato G, Pedroncelli AM, Baldelli R, Grottoli S, Gasco V et.al. Gender-and age-related differences in the endocrine parameters of acromegaly. J Endocrinol Invest. 2002 Jun; 25(6): 532-8. DOI: 10.1007/BF03345496
Colao A, Grasso LF, Giustina A, Melmed S, Chanson P, Pereira AM et al. Nat Rev Dis Primers. 2019 Oct 21;5(1):72. doi: 10.1038/s41572-019-0129-5DOI: 10.1038/s41572-019-0071-6
Yarman S, Ogret YD, Oguz FS. Do the aryl hydrocarbon receptor interacting protein variants (Q228K and Q307R) play a role in patients with familial and sporadic hormone-secreting pituitary adenomas. Genetic testing and molecular biomarkers, 19(7),394–398. doi: 10.1089/gtmb.2014.0333
García-Guzmán B, Portocarrero-Ortiz L, Dorantes-Argandar AA, Mercado M. Hereditary Pituitary Tumor Syndromes: Genetic and Clinical Aspects. Rev Invest Clin., 2020; 72(1): 8-18. DOI: 10.24875/RIC.19003186
Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA et.al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab., 2007 May 1; 92(5): 1891-6. DOI: 10.1126/science.1126100.
Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A et.al . Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science, 2006 May 26; 312(5777): 1228-30. DOI: 10.1126/science.1126100
Georgitsi M, Heliovaara E, Paschke R, Kumar AV, Tischkowitz M, Vierimaa O et.al . Large genomic deletions in AIP in pituitary adenoma predisposition. J Clin Endocrinol Metab., 2008 Oct 1; 93(10): 4146-51.doi.org/10.1210/jc.2008-1003
Rowlands CJ, Staskal DF, Gollapudi B, Budinsky R. The human AHR: identification of single nucleotide polymorphisms from six ethnic populations. Pharmacogenet Genomics. 2010 May 1; 20(5): 283-90. DOI: 10.1097/fpc.0b013e32833605f8
Shah SS, Aghi MK. The Role of Single-Nucleotide Polymorphisms in Pituitary Adenomas Tumorigenesis. Cancers (Basel). 2019 Dec 9;11(12):1977.DOI: 10.3390/cancers11121977
Chen B, Liu P, Hujber EJ, Li Y, Jorgensen EM, Wang ZW. AIP limits neurotransmitter release by inhibiting calcium bursts from the ryanodine receptor. Nat Commun. 2017 Nov 9; 8(1): 1-4. DOI: 10.1038/s41467-017-01704-z
Salvatori R, Radian S, Diekmann Y, Iacovazzo D, David A, Gabrovska P et.al. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism. Eur J Rndocrinol., 2017 Sep 1; 177(3): 257-66. doi: 10.1530/EJE-17-0293
Schernthaner-Reiter MH, Trivellin G, Stratakis CA. Interaction of AIP with protein kinase A (cAMP-dependent protein kinase). Hum Mol Genet., 2018 Aug 1; 27(15): 2604-13. DOI: 10.1093/hmg/ddy166
Bilbao Garay I, Daly AF, Egaña Zunzunegi N, Beckers A. Pituitary Disease in AIP Mutation-Positive Familial Isolated Pituitary Adenoma (FIPA): A Kindred-Based Overview. J Clin Med., 2020 Jun; 9(6): 2003. doi: 10.3390/jcm9062003
Hara T, Kanasaki H, Oride A, Moriyama M, Kyo S. Case of a woman with acromegaly whose presenting complaint was prolonged post‐partum amenorrhea. J Obstet Gynaecol Res., 2016 Oct; 42(10): 1379-84. DOI: 10.1111/jog.13065
Kelberman, D., Rizzoti, K., Lovell-Badge, R., Robinson, I. C., & Dattani, M. T. (2009). Genetic regulation of pituitary gland development in human and mouse. Endocr. Rev , 30(7): 790–829. https://doi.org/10.1210/er. 2009-0008
23. Mahmood AR, Abdullah MR, Abdullah KT. Determination of Some Biochemical Parameters of Acromegalic Patients with Type 2 Diabetes Mellitus. J Pharm Sci., 2019 Mar 1; 11(3): 787-90. https://www.jpsr.pharmainfo.
Gadelha MR, Kasuki L, Lim DS, Fleseriu M. Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocr Rev., 2019 Feb; 40(1): 268-332. DOI: 10.1210/er.2018-00115
25. Bollerslev J, Heck A, Olarescu NC. Management of endocrine disease: individualised management of acromegaly. Eur J Endocrinol . 2019 Aug 1; 181(2): R57-71. DOI: 10.1530/EJE-19-0124
Clemmons DR, Chihara K, Freda PU, Ho KK, Klibanski A, Melmed S et.al. Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm. J Endocrinol Metab., 2003 Oct 1; 88(10): 4759-67. https://doi.org/10.1210/jc.2003-030518
Alexandraki KI, Grossman AB. Management of hypopituitarism. J Clin Med. 2019 Dec; 8(12):2153. DOI: 10.3390/jcm8122153
Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004 Feb 1; 89(2): 667-74. DOI: 10.1210/jc.2003-031199
Bilbao Garay I, Daly AF, Egaña Zunzunegi N, Beckers A. Pituitary Disease in AIP Mutation-Positive Familial Isolated Pituitary Adenoma (FIPA): A Kindred-Based Overview. J Clin Med. 2020 Jun; 9(6): 2003. doi: 10.3390/jcm9062003
Jemel M, Alaya W, Boubaker F, Berrich O, Zantour B .Pituitary Apoplexy. InPituitary Diseases Intech Open. London, UK. Published: March 13th 2019, DOI: 10.5772/intechopen.77270
31. Marques P, Caimari F, Hernández-Ramírez LC, Collier D, Iacovazzo D, Ronaldson A, Magid K, Lim CT, Stals K, Ellard S, and Grossman AB. Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors. J Endocrinol Metab., 2020 Jun 1; 105(6): e2247-60 https://doi.org/10.1210/clinem/dgaa040.
Ciresi A, Guarnotta V, Campo D, Giordano C. Hepatic steatosis index in acromegaly: correlation with insulin resistance regardless of the disease control. Int J Endocrinol., 2018 Dec 19; 2018. DOI: 10.1155/2018/5421961
Lewiński A, Marcinkowska M, Brzeziańska E, Jeziorowska A, Włoch J, Brzeziński J. Expression of Insulin‐like Growth Factor I (IGF‐I) Gene and of Genes for IGF‐Binding Proteins 1, 2, 3, 4 (IGFBP‐1—IGFBP‐4) in Non‐neoplastic Human Thyroid Cells and in Certain Human Thyroid Cancers. Effect of Exogenous IGF‐I on This Expression. Endocr Res., 2004 Jan 1; 30(1): 47-59. DOI: 10.1081/erc-120028484
Karagiannis A, Kassi E, Chatzigeorgiou A, Koutsilieris M. IGF Bioregulation System in Benign and Malignant Thyroid Nodular Disease: A Systematic Review. In Vivo., 2020 Nov-Dec; 34(6): 3069-3091. DOI: 10.21873/invivo.12141
Wolinski K, Czarnywojtek A, Ruchala M. Risk of thyroid nodular disease and thyroid cancer in patients with acromegaly–meta-analysis and systematic review. PLoS One. 2014 Feb 14; 9(2): e88787. DOI: 10.1371/journal.pone.0088787
dos Santos MC, Nascimento GC, Nascimento AG, Carvalho VC, Lopes MH, Montenegro R et.al. Thyroid cancer in patients with acromegaly: a case–control study. Pituitary. 2013 Mar; 16(1):109-14. DOI: 10.1007/s11102-012-0383-y
37. Dhefer IH, Rudha Abass SA, Ahmed NS. Comparative Study of Aromatase Activity Level in Male Patients with Active Acromegaly. Int J Chem Sci. 2017; 15(2): 131. www.tsijournals.com | June-2017
Padova G, Borzì G, Incorvaia L, Siciliano G, Migliorino V, Vetri M, et al.Prevalence of osteoporosis and vertebral fractures in acromegalic patients. Clin Cases Miner Bone Metab. 2011 Sep-Dec; 8(3): 37–43 PMID: 22461828 PMCID: PMC3279059
Verhelst J, Velkeniers B, Maiter D, Haentjens P, T’Sjoen G, Rietzschel E et.al. Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels: insights from the Belgian registry of acromegaly. Eur J Endocrinol., 2013 Jan 17; 168(2): 177-84. DOI: 10.1530/EJE-12-0753
Reid IR. Relationships between fat and bone. Osteoporos Int., 2008 May; 19(5):595-606. DOI: 10.1007/s00198-007-0492-z
Berg C, Petersenn S, Lahner H, Herrmann BL, Buchfelder M, Droste M et.al. Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab., 2010 Aug 1; 95(8):3648-56. DOI: 10.1210/jc.2009-2570
Khaleel Fayhaa M, AL-Shammri Ihsan A, Mohammed Nour AL-Huda G. Estimation of Testosterone, Estradiol and some Markers in Sera of Iraqi Patients with Benign Prostatic Hyperplasia.: Fayhaa M.Khaleel|Ihsan A.AL-Shammri|Nour AL-Huda G. Mohammed. Baghdad Sci J. Daly AF, Rostomyan L, Betea D, Bonneville JF, Villa C, Pellegata NS, et al.,. AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients. Endocrine Connections J., 2019 Apr 1; 8(4): 367-77. DOI: 10.1530/EC-19-0004, 2013; 10(4), 1162-1171.
Hashim Nidhal A, Khalifa Ahmed A, Mohammed Mukhtar K.. Evaluation of Sex Hormone Levels in B enign Prostatic Hyperplasia Patients Treated with 5 Alpha-Reductase Inhibitor (Finasteride) in Amara city/Iraq. Baghdad Sci J., 2020; 17(1): 1-8. https://doi.org/10.21123/bsj.2020.17.1.0001
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