Study of HLA-G gene 14-bp ins/del and codon 93 (CAC/CAT) polymorphisms association with spontaneous abortion in a Tunisian population

Sana Belkahla(1), Insha Nahvi(2), Hena Khan(3),


(1) Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al-Ahsa, 31982,
(2) Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
(3) Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
Corresponding Author

Abstract


In the recent years, spontaneous abortion (SA) frequency increased awareness about medical and social-economic related problems. Human leukocyte antigen-G (HLA-G) is a non-classic HLA I molecule initially described in trophoblastic tissue in foeto-maternal interface. HLA-G polymorphism association with SA has been extensively studied. One amongst the foremost studied variants was HLA-G 14-bp Insertion (Ins)/Deletion (Del) polymorphism. Nevertheless, such a study was not performed in Tunisian population yet. We aim to investigate two HLA-G polymorphisms, 14-bp Ins/Del 3'UTR, and for the first time, codon 93 (CAC/CAT) polymorphisms association with SA risk in the Tunisian population. The results revealed HLA-G 14-bp Ins/Del polymorphism and CIns haplotype association with SA. No association of the HLA-G codon 93 (CAC/CAT) polymorphism to SA was observed. Considering both polymorphism together, female's homozygosity for 14-bp Ins/Del and for codon 93 (CAC/CAT) polymorphism may increase the risk of SA susceptibility. (Afr J Reprod Health 2022; 26[1]: 103-109)

References


Rafael GV , Paulo RS, Sibelle BM, Eni PB, Joandrei

SS, Alessandro P and Maria GB. Association of HLA-G alleles and 3' UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples. Human Immunology 2011; 72: 479-485.

Jun G , Yubei H, Lei Y, Zhengqiang X, Shuhong S, Juan

Y, Li K and Wengang Q . Association between abortion and breast cancer : an updated systematic review and meta-analysis based on prospective studies. Cancer Causes Control. 2015 ; 6 :811-9.

Carlo T, Adalgisa P , Nicoletta DS , Emilio P and Asgerally

F . Endometrial Immune Dysfunction in Recurrent Pregnancy Loss. Int J Mol Sci. 2019 ; 21:5332.

Szekeres-Bartho J. Immunological relationship between the

mother and the fetus. Int Rev Immunol. 2002; 21(6):471-95.

Gordana L, Tamara G , Lana GG , Marin D, Herman H and

Daniel R. Assessing whether progesteronematured dendritic cells are responsible for retention of fertilization products in missed abortion. Med Hypotheses 2018; 118:169-173.

Aifen Lin and Wei-Hua Yan, Heterogeneity of HLA-G

Expression in Cancers: Facing the Challenges. Frontiers in Immunology, 2018 (9).

Silvia G. HLA-G-Mediated Immune Tolerance: Past and

New Outlooks. Front Immunol. 2016;7:653.

Nathalie RF, Philippe M, Catherine M, Joël Le M and

Edgardo DC. Expression of tolerogenic HLA-G

molecules in cancer prevents antitumor responses.

Semin Cancer Biol. 2007, 17(6):413-421.

Brugière O, Thabut G, Pretolani M, Krawice-Radanne I, Dill C, Herbreteau A, Poras I, Moreau P, Colombat M, Danel C, Dehoux M, Fournier M, Carosella ED and Rouas-Freiss N.

Immunohistochemical study of HLA-G expression

in lung transplant recipients. Am J Transplant 2009;

:1427–1438.

Vera R, Diana B, Andreas W, Petra M, Thomas G, Richard V and Hans GW. Soluble total human leukocyte antigen class I and human leukocyte antigen-G molecules in kidney and kidney/pancreas transplantation. Hum Immunol, 2009; 70:995–999.

Frederic D , Diego D, Vito P, Massimo G, Fabio M and

Antoine D, HLA-G in organ transplantation: towards

clinical applications. Cell Mol Life Sci. 2011; 68(3):397-404.

Tess M , Lisa L, Olaf MD, Jan L , Frans C and Kitty B.

HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis. Human Immunology, 2015; 76(5), 362–373.

Wei F, Zhongying H, Shangwei L and Zhun X. The HLAG 14-bp polymorphism and recurrent implantation failure: a meta-analysis. Journal of Assisted Reproduction and Genetics, 2017; 34(11):1559-65

Franziska MW, Christoph W , Peter T , Ralph MW and

Wolfgang W. European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment. International Journal of Molecular Sciences, 2019; 20(8), 1830.

O'Brien M , McCarthy T, Jenkins D, Paul P, Dausset

J, Carosella ED and Moreau P. Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLAG gene in susceptibility to the disease. Cell Mol Life Sci, 2001; 58(12-13), 1943–49.

Hviid TV, Hylenius S, Hoegh AM, Kruse C and Christiansen OB. HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens, 2002; 60:122–132.

Matte C, Lacaille J, Zijenah L, Ward B and Roger M the

ZVITAMBO Study Group. HLA-G and HLA-E Polymorphisms in an Indigenous African Population. Human Immunology, 2000; 61:1150-1156.

Shankarkumar U, Shankarkumar A, Chedda A and Ghosh

K. Role of 14-bp deletion/insertion polymorphism in

exon 8 of the HLA-G gene in recurrent spontaneous

abortion patients. Journal of Human Reproductive Sciences, 2011; 4(3): 143.

Fateme A and Morteza S . Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran. Journal of Immunotoxicology, 2015; 13 (2) 249-54.

Moniek C, Iris N, Milo C, Jos D, Marijke SG, Jacqueline A, Hanneke M K, Janine A S, Carin van der K, Esther F, Geert WH, Marie-Louise H, Frans Claas, Sebastiaan H and Michael E.Increased HLAG Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels. International Journal of Molecular Sciences, 2019; 20(3): 625.

Aruna M , Sirisha P, Bhaskar SA, Tarakeswari

S, Thangaraj K and Reddy BM. Role of 14-bp

insertion/deletion polymorphism in HLA-G among

Indian women with recurrent spontaneous abortions.

Tissue Antigens 2011; 77(2): 131–5.

Al Omar YS, Mansour L , Alkhuriji AF, Alwasel S and AlQahtani S. Genetic association between the HLA-G

-bp insertion/deletion polymorphism and the

recurrent spontaneous abortions in Saudi Arabian

women. Genetics and Molecular Research, 2015;

(1): 286–293.

Kalotra V, Lall M, Verma IC and A Kaur. The HLA-G

bp insertion/deletion polymorphism and its

association with soluble HLA-G levels in women

with recurrent miscarriages. HLA, 2018; 91(3): 167-

Ishitani A and Geraghty DE. Alternative splicing of HLAG transcripts yields proteins with primary structures

resembling both class I and class II antigens. Proc.

Natl. Acad. Sci. USA 1992, 89, 3947–51.

Carosella ED, Benoit F, Nathalie RF and Moreau P.

Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood, 2008; 111, 4862–70.

Margit HL and Thomas VFH. Human leukocyte antigen-G

polymorphism in relation to expression, function,

and disease. Hum Immunol, 2009;70:1026–1034.

Giada A and Silvia G. HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives. Frontiers in Immunology, 2020; 11, 1178.

Chen XY, Yan WH, Lin A, Xu HH, Zhang JG and Wang

X. The 14 bp deletion polymorphisms in HLA-G gene play an important role in the expression of soluble HLA-G in plasma.Tissue Antigens, 2008; 72, 335-41

Philippe R, Magali D, Gaël M, Céline M and Carosella ED.

The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol, 2003, 64 , 1005-10.

Castelli E, Moreau P, Alynne C, Celso MJ, Luciana VC, Layale Y, Silvana G, Carosella ED and Eduardo AD. In silico analysis of microRNAS targeting the HLA-G 3′ untranslated region alleles and haplotypes. Human Immunology, 2009;70(12):1020–25.

Inès Z, Roberta R, Aicha B, Ahmed BL , Nour Z , Dario

DL , Henda T and Daria B. sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion. Human Immunology, 2016; 77(4): 342-5.

Inès Z, Olfa D, Nour Z , Refaat S, Nadia B ,Amna BH , Hamza BY, Ahmed BL, Wafa B, Hela R, Amel M and Hanene C. Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population. Immunologic Research, 2016; 64(4): 961–968.

Sine H , Anne-Marie NA, Mads M and Thomas VFH.

Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads. Molecular Human Reproduction, 2004; 10(4): 237–46.

Rebmann V , van der Ven K, Pässler M, Pfeiffer K, Krebs

D and Grosse-Wilde H. Association of soluble HLA‐

G plasma levels with HLA‐G alleles. Tissue Antigens, 2001; 57(1): 15-21.

Carosella ED , Rouas-Freiss N, Diana TR , Moreau P and

Joel LM. HLA-G. An immune checkpoint molecule.

Adv Immunol, 2015; 127, 33– 144


Full Text: PDF

Article Metrics

Abstract View : 568 times
PDF Download : 306 times

Refbacks

  • There are currently no refbacks.