Interleukin-1 Receptor Antagonist (IL-1RN) Gene Variable Number Tandem Repeats (VNTR) Polymorphism Association in men Infertility in Erbil City /Kurdistan Iraq

Main Article Content

Yassin Kareem Amin
Ashti M. Said
Ahmed A. Al-Naqshbandi
Saeed Ghulam


The interleukin-1 family has multifaceted roles in men٫s reproductive syste. Out  of these is interleukin-1 receptor antagonist (IL-1RN) which exists in men gonads, and in case of infection and inflammatory process, its activity is increased.  The current study aims to verify a possible linkage of Variable Number Tandem Repeat (VNTR) polymorphism of the IL-1RN gene with human men infertility. The study groups enrolled included 100 infertile men and 100 fertile and healthy men. Their seminal fluids were subjected to analysis. Also peripheral blood samples were collected for the assessment or detection of polymorphic Variable Number  Tandem Repeats (VNTR) polymorphism of interleukin-1 receptor antagonist gene (IL-1RN). Two alleles, namely IL-1RN1 allele corresponding to 410bp fragment and IL-11RN2 that corresponding to 240bp fragments,  are a marker for human men infertility, detected by PCR technique. The results delineated a high frequency of IL-1RN2 allelic gene variants (26%), and two VNTR allelic gene variants carriers IL-1RN1 and IL-1RN2 (16%) among  infertile men with significant impacts on sperm motility and morphology (P< 0.000-0.002) respectively. This prospective study inKurdistan region (Erbil –Iraq)  defined a significant impact of VNTR polymorphism of IL-1RN gene in the etiology of men infertility especially on sperm motility and morphology; particularly carriers of IL-1RN2 allelic variants


Download data is not yet available.

Article Details

How to Cite
Amin YK, Said AM, Al-Naqshbandi AA, Ghulam S. Interleukin-1 Receptor Antagonist (IL-1RN) Gene Variable Number Tandem Repeats (VNTR) Polymorphism Association in men Infertility in Erbil City /Kurdistan Iraq. Baghdad Sci.J [Internet]. [cited 2021Mar.4];18(3):0438. Available from:


-Abu Elheija M, Dyomin V, Ganaiem M, Lunenfeld E, Vardy NS, Huleihel M. Distinct expression of interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist in testicular tissues and cells from human biopsies with normal and abnormal histology. J Interferon Cytokine Res. 2011;31(4):401-8.

-Rafatmanesh A, Nikzad H, Ebrahimi A, Karimian M, Zamani T. Association of the c.-9C>T and c.368A>G transitions in H2BFWT gene with male infertility in an Iranian population. Andrologia. 2018;50(1).

-Ren Z, Ren P, Yang B, Fang K, Ren S, Liao J, et al. MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis. PLoS One. 2017;12(1):e0169789.

-Tarin JJ, Garcia-Perez MA, Hamatani T, Cano A. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases. Reprod Biol Endocrinol. 2015;13:31.

-Rebourcet D, Darbey A, Monteiro A, Soffientini U, Tsai YT, Handel I, et al. Sertoli Cell Number Defines and Predicts Germ and Leydig Cell Population Sizes in the Adult Mouse Testis. Endocrinology. 2017;158(9):2955-69.

-Bracke A, Peeters K, Punjabi U, Hoogewijs D, Dewilde S. A search for molecular mechanisms underlying male idiopathic infertility. Reprod Biomed Online. 2018;36(3):327-39.

-Havrylyuk A, Chopyak V, Boyko Y, Kril I, Kurpisz M. Cytokines in the blood and semen of infertile patients. Cent Eur J Immunol. 2015;40(3):337-44.

-Fraczek M, Kurpisz M. Cytokines in the male reproductive tract and their role in infertility disorders. J Reprod Immunol. 2015;108:98-104.

-Ad’hiah AH, Hessan EB, Shahab BA. Interleukin-1 single nucleotide polymorphisms as risk factor for susceptibility of inflammatory bowel disease: an Iraq Arab population based study. Alexandria J. Med.2019;55(1):1-6.

-Al-Naseri MA, Salman ED, Ad’hiah AH. Serum level and single nucleotide gene polymorphism of interleukin-1receptor antagonist in a sample of Iraq multiple sclerosis patients. Bio Genet J.


-Ford WC. Comments on the release of the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen. Asian J Androl. 2010;12(1):59-63.

-Ganaiem M, AbuElhija M, Lunenfeld E, Cherniy N, Weisze N, Itach SB, et al. Effect of interleukin-1 receptor antagonist gene deletion on male mouse fertility. Endocrinology. 2009;150(1):295-303.

-Fiskerstrand CE, Lovejoy EA, Quinn JP. An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett. 1999;458(2):171-4.

- Hales DB, Diemer T, Hales KH. Role of cytokines in testicular function. Endocrine. 1999;10(3):201-17.

- Soder O, Sultana T, Jonsson C, Wahlgren A, Petersen C, Holst M. The interleukin-1 system in the testis. Andrologia. 2000;32(1):52-5.

- Al-Marzoqi AH, Hussein, HJ, Al-Janabi HSO, Ibraheem HK, Al-Taee ZM. Role of interleukin 1, IL-18 and tumor necrosis factor alpha levels in seminal plasma of infertile males in Hillah patients. J. Bio Agr Health. 2013;3(3):165-171.

-Zamani-Badi T, Nikzad H, Karimian M. IL-1RA VNTR and IL-1alpha 4845G>T polymorphisms and risk of idiopathic male infertility in Iranian men: A case-control study and an in silico analysis. Andrologia. 2018;50(9):e13081.

-Jaiswal D, Trivedi S, Singh R, Dada R, Singh K. Association of the IL1RN gene VNTR polymorphism with human male infertility. PLoS One. 2012;7(12):e51899.

-Hurme M, Santtila S. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;28(8):2598-602.

-Cauci S, Buligan C, Rocchi F, Salvador I, Xodo L, Stinco G. Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma. Oncol Lett. 2019;18(6):5759-68.

-Singh M, Mansuri MS, Jadeja SD, Marfatia YS, Begum R. Association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism with vitiligo susceptibility in Gujarat population. Indian J Dermatol Venereol Leprol. 2018;84(3):285-91.

-He Y, Peng S, Xiong W, Xu Y, Liu J.

Association between polymorphism of interleukin-1 beta and interleukin-1 receptor antagonist gene and asthma risk: a meta-analysis. Sci. World J.2015;2015:685684.

-Jamali S, Karimian M, Nikzad H, Aftabi Y. The c-190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia. Mol Biol Rep. 2016;43(8):795-802.

-Babushkina NP, Kucher AN. Functional role of VNTR polymorphism of human genes. Genetika. 2011; 47(6):725-34.

-Gremlich S, Fratta S, Rebellato E, Uras R, Reymondin D, Damnon F, et al. Interleukin-1 receptor antagonist gene (IL-1RN) polymorphism is a predictive factor of clinical pregnancy after IVF. Hum Reprod. 2008;23(5):1200-6.

-Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet. 1993;91(4):403-4.

-Karimian M, Hosseinzadeh Colagar A . Methionine synthase A2756G transition might be a risk factor for male infertility: Evidence from seven case-control studies. Mol Cell Endocrinol. 2016;425:1-10.

-Nikzad H, Karimian M, Sareban K, Khoshsokhan M, Hosseinzadeh Colagar A MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis. Reprod Biomed Online. 2015;31(5):668-80.

-Le Fur S, Auffray C, Letourneur F, Cruaud C, Le Stunff C, Bougneres P. Heterogeneity of class I INS VNTR allele association with insulin secretion in obese children. Physiol Genomics. 2006; 25(3):480-4.

-Khoshroo M, Khamseh ME, Amir Zargar AA, Malek M, Falak R, Shekarabi M. The Relationship between insulin variable number of tandem repeats (INS-VNTR) -23 A/T and cytotoxic Tlymphocyte associated protein-4 (CTLA-4) +49 A/G polymorphisms with islet autoantibodies in persons with diabetes. Med J Islam Repub Iran. 2017;31:83.

-Al-Safar H, Kamal W, Hassoun A, Almahmeed W, Rais N. Combined association analysis of interleukin 1-receptor antagonist (IL-1RN) variable number of tandem repeat (VNTR) and Haptoglobin 1/2 polymorphisms with type 2 diabetes mellitus risk. J Diabetes Metab Disord. 2015;15:10.

-Zorina-Lichtenwalter K, Meloto CB, Khoury S, Diatchenko L. Genetic predictors of human chronic pain conditions. Neuroscience. 2016;338:36-62.

-Van Dyck CH, Malison RT, Jacobsen LK, Seibyl JP, Staley JK, Laruelle M, et al. Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. J Nucl Med. 2005;46(5):745-51.

-Jahantigh D, Hosseinzadeh Colagar A. XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies. Int J Endocrinol. 2017;2017:4795076.

-Say YH. The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications. J Physiol Anthropol. 2017;36(1):25.

-Strandberg L, Lorentzon M, Hellqvist A, Nilsson S, Wallenius V, Ohlsson C, et al. Interleukin-1 system gene polymorphisms are associated with fat mass in young men. J Clin Endocrinol Metab. 2006;91(7):2749-54.

-Potts JM, Sharma R, Pasqualotto F, Nelson D, Hall G, Agarwal A. Association of ureaplasma urealyticum with abnormal reactive oxygen species levels and absence of leukocytospermia. J Urol. 2000;163(6):1775-8.