Association of adenosine deaminase (ADA) gene 4223A/C polymorphism with obesity in Ardabil, Iran

Authors
1 Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran
2 Department of Genetics, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
Abstract
Objective: Adenosine deaminase (ADA) is a polymorphic enzyme which has an important role in the modulation of insulin bioactivity. The ADA gene polymorphism seems to contribute to the degree of obesity. The aim of this study is to examine the role of ADA gene polymorphism in randomly selected obese subjects from Ardabil Province, Iran.
Methods: This case-control study included 170 obese subjects (BMI ≥30) and 200 healthy (BMI ≤30) subjects recruited from Ardabil province's cities. Before the study, these individuals provided approximately 5 ml of blood for molecular tests. We extracted DNA from the blood samples using a standard phenol chloroform procedure. The region that contained the ADA, 4223A/C polymorphism was genotyped by PCR and restriction fragment length polymorphism PCR-RFLP, and the collected data were analyzed using the X2 test.
Results: The obese group had significantly increased allele A frequency compared with the control (p=0.034).
Conclusion: Our findings suggest a role for the ADA gene in the obesity. Larger studies of other populations are required to confirm these findings.

Keywords


[1] Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka DC, Esko T, Fall T, Ferreira T, Gustafsson S, Kutalik Z, Luan J, Mägi R, Randall JC, Winkler TW, Wood AR, Workalemahu T, Faul JD, Smith JA, Zhao JH, Zhao W, Chen J, Fehrmann R, Hedman ÅK, Karjalainen J, Schmidt EM, Absher D, Amin N, Anderson D, Beekman M, Bolton JL, Bragg-Gresham JL, Buyske S, Demirkan A, Deng G, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Goel A, Gong J, Jackson AU, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Leach IM, Medina-Gomez C, Medland SE, Nalls MA, Palmer CD, Pasko D, Pechlivanis S, Peters MJ, Prokopenko I, Shungin D, Stančáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet-Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Isaacs A, Albrecht E, Ärnlöv J, Arscott GM, Attwood AP, Bandinelli S, Barrett A, Bas IN, Bellis C, Bennett AJ, Berne C, Blagieva R, Blüher M, Böhringer S, Bonnycastle LL, Böttcher Y, Boyd HA, Bruinenberg M, Caspersen IH, Chen YI, Clarke R, Daw EW, de Craen AJM, Delgado G, Dimitriou M, Doney ASF, Eklund N, Estrada K, Eury E, Folkersen L, Fraser RM, Garcia ME, Geller F, Giedraitis V, Gigante B, Go AS, Golay A, Goodall AH, Gordon SD, Gorski M, Grabe HJ, Grallert H, Grammer TB, Gräßler J, Grönberg H, Groves CJ, Gusto G, Haessler J, Hall P, Haller T, Hallmans G, Hartman CA, Hassinen M, Hayward C, Heard-Costa NL, Helmer Q, Hengstenberg C, Holmen O, Hottenga JJ, James AL, Jeff JM, Johansson Å, Jolley J, Juliusdottir T, Kinnunen L, Koenig W, Koskenvuo M, Kratzer W, Laitinen J, Lamina C, Leander K, Lee NR, Lichtner P, Lind L, Lindström J, Lo KS, Lobbens S, Lorbeer R, Lu Y, Mach F, Magnusson PKE, Mahajan A, McArdle WL, McLachlan S, Menni C, Merger S, Mihailov E, Milani L, Moayyeri A, Monda KL, Morken MA, Mulas A, Müller G, Müller-Nurasyid M, Musk AW, Nagaraja R, Nöthen MM, Nolte IM, Pilz S, Rayner NW, Renstrom F, Rettig R, Ried JS, Ripke S, Robertson NR, Rose LM, Sanna S, Scharnagl H, Scholtens S, Schumacher FR, Scott WR, Seufferlein T, Shi J, Smith AV, Smolonska J, Stanton AV, Steinthorsdottir V, Stirrups K, Stringham HM, Sundström J, Swertz MA, Swift AJ, Syvänen AC, Tan ST, Tayo BO, Thorand B, Thorleifsson G, Tyrer JP, Uh HW, Vandenput L, Verhulst FC, Vermeulen SH, Verweij N, Vonk JM, Waite LL, Warren HR, Waterworth D, Weedon MN, Wilkens LR, Willenborg C, Wilsgaard T, Wojczynski MK, Wong A, Wright AF, Zhang Q; LifeLines Cohort Study, Brennan EP, Choi M, Dastani Z, Drong AW, Eriksson P, Franco-Cereceda A, Gådin JR, Gharavi AG, Goddard ME, Handsaker RE, Huang J, Karpe F, Kathiresan S, Keildson S, Kiryluk K, Kubo M, Lee JY, Liang L, Lifton RP, Ma B, McCarroll SA, McKnight AJ, Min JL, Moffatt MF, Montgomery GW, Murabito JM, Nicholson G, Nyholt DR, Okada Y, Perry JRB, Dorajoo R, Reinmaa E, Salem RM, Sandholm N, Scott RA, Stolk L, Takahashi A, Tanaka T, van 't Hooft FM, Vinkhuyzen AAE, Westra HJ, Zheng W, Zondervan KT; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium, Heath AC, Arveiler D, Bakker SJL, Beilby J, Bergman RN, Blangero J, Bovet P, Campbell H, Caulfield MJ, Cesana G, Chakravarti A, Chasman DI, Chines PS, Collins FS, Crawford DC, Cupples LA, Cusi D, Danesh J, de Faire U, den Ruijter HM, Dominiczak AF, Erbel R, Erdmann J, Eriksson JG, Farrall M, Felix SB, Ferrannini E, Ferrières J, Ford I, Forouhi NG, Forrester T, Franco OH, Gansevoort RT, Gejman PV, Gieger C, Gottesman O, Gudnason V, Gyllensten U, Hall AS, Harris TB, Hattersley AT, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Homuth G, Hovingh GK, Humphries SE, Hunt SC, Hyppönen E, Illig T, Jacobs KB, Jarvelin MR, Jöckel KH, Johansen B, Jousilahti P, Jukema JW, Jula AM, Kaprio J, Kastelein JJP, Keinanen-Kiukaanniemi SM, Kiemeney LA, Knekt P, Kooner JS, Kooperberg C, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Marchand LL, Lehtimäki T, Lyssenko V, Männistö S, Marette A, Matise TC, McKenzie CA, McKnight B, Moll FL, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Madden PAF, Pasterkamp G, Peden JF, Peters A, Postma DS, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ridker PM, Rioux JD, Ritchie MD, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schunkert H, Schwarz PEH, Sever P, Shuldiner AR, Sinisalo J, Stolk RP, Strauch K, Tönjes A, Trégouët DA, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Völker U, Waeber G, Willemsen G, Witteman JC, Zillikens MC, Adair LS, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bornstein SR, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PIW, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hui J, Hunter DJ, Hveem K, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, März W, Melbye M, Metspalu A, Moebus S, Munroe PB, Njølstad I, Oostra BA, Palmer CNA, Pedersen NL, Perola M, Pérusse L, Peters U, Power C, Quertermous T, Rauramaa R, Rivadeneira F, Saaristo TE, Saleheen D, Sattar N, Schadt EE, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Thorsteinsdottir U, Stumvoll M, Tuomilehto J, Uitterlinden AG, Uusitupa M, van der Harst P, Walker M, Wallaschofski H, Wareham NJ, Watkins H, Weir DR, Wichmann HE, Wilson JF, Zanen P, Borecki IB, Deloukas P, Fox CS, Heid IM, O'Connell JR, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, Franke L, Frayling TM, McCarthy MI, Visscher PM, Scherag A, Willer CJ, Boehnke M, Mohlke KL, Lindgren CM, Beckmann JS, Barroso I, North KE, Ingelsson E, Hirschhorn JN, Loos  RJF, Speliotes EK. Genetic studies of body mass index yield new insights for obesity biology. Nature 2015; 518(7538): 197-206.
[2] Loos RJ. Genetic determinants of common obesity and their value in prediction. Best Pract Res Clin Endocrinol Metab 2012; 26(2): 211-26.
[3] Tabatabaei-Malazy O, Khodaeian M, Amoli MM. Association between Genetic Variants and Obesity in Iranian Population: Review Article. Iranian J Publ Health 2014; 43(Suppl 1): 71-82.
[4] Wiginton DA, Adrian GS, Friedman RL, Suttle DP, Hutton JJ. Cloning of cDNA sequences of human adenosine deaminase. Proc Natl Acad Sci U S A 1983; 80(24): 7481-5.
[5] Petersen MB, Tranebjaerg L, Tommerup N, Nygaard P, Edwards H. New assignment of the adenosine deaminase gene locus to chromosome 20q13 X 11 by study of a patient with interstitial deletion 20q. J Med Genet 1987; 24(2): 93-6.
[6] Chung FZ, Weber HW, Appleman MM. Extensive but reversible depletion of ATP via adenylate cyclase in rat adipocytes. Proc Natl Acad Sci U S A 1985; 82(6): 1614-7.
[7] Rashidy-Pour A, Malek M, Eskandarian R, Ghorbani R. Obesity in the Iranian population. Obes Rev 2009; 10(1): 2-6.
[8] Bottini E, Gloria-Bottini F. Adenosine deaminase and body mass index in non-insulin-dependent diabetes mellitus. Metabolism 1999; 48(8): 949-51.
[9] Hoshino T, Yamada K, Masuoka K, Tsuboi I, Itoh K, Nonaka K, Oizumi K. Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus. Diabetes Res Clin Pract 1994; 25(2): 97-102.
[10] Xu B, Berkich DA, Crist GH, LaNoue KF. A1 adenosine receptorimprove antagonism glucose tolerance in Zucker rats. American Journal of Physiology-Endocrinology and Metabolism 1998; 274(2): E271-9.
[11] Heseltine L, Webster JM, Taylor R. Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes. Mol Cell Biochem 1995; 144(2): 147-51.
[12] Amoli MM, Amiri P, Namakchian M, Saeid Nejad R, Fakhrzadeh H, Heshmat R, Mehraban N, Aryani Kashani A, Yaghmaie P, Tavakkoly Bazzaz J, Larijani B. Adenosine deaminase gene polymorphism is associated with obesity in Iranian population. Obes Res Clin Pract 2007; 1(3): 173-7.
[13] Yaghoubi H, Haghi M, Solhi S. Detection of CXCL5 Gene Polymorphism with Diabetes in Ardabil Province. J Ardabil Univ Med Sci 2013; 13(4): 438-43. (Persian)