Investigation of the association between HLA-G polymorphisms and obesity



Obesity, HLA-G, Polymorphism


Background/Aim: Obesity is a global public health problem seen worldwide, with an increasing prevalence over time. Obesity is a multifactorial disease affected by both genetic and environmental factors. It is accompanied by many other diseases, the most important of which are immune system disorders. Induction of suppression of HLA-G molecule T and B lymphocytes is associated with natural killer cells and antigen-presenting cells. The HLA-G gene shows functional polymorphisms in regulatory regions. The HLA-G gene is slightly more conserved compared to other HLA genes, both in the same population and among different populations. The aim of this research is to determine the association of HLA-G gene polymorphisms (14 bp insertion/deletion 3 'UTR (rs66554220), rs41557518, and rs1063320) with obesity. Methods: Fifty normal (BMI ≤30) individuals having no obesity-related chronic disorder, and 50 obese (BMI≥ 30) individuals were included in the study. After DNA isolation, PCR and PCR-RFLP methods were used for genotyping. Results: The genotype frequencies of HLA-G polymorphisms (rs66554220, rs41557518, and rs1063320) in the normal and obese groups were compared, and as a result, no significant difference was found (P>0.05). Conclusion: No significant association was found between rs66554220, rs41557518, and rs1063320 polymorphisms and obesity.


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Karpe F, Lindgren CM. Obesity—On or Off? N Engl J Med. 2016;374(15):1486-8.

O’Rahilly S. Human genetics illuminates the paths to metabolic disease. Nature. 2009;462(7271):307.

George A, Bray MD. Risks of Obesity. Endocrinol Metab Clin North Am. 2003;32:787-804.

Xia Q, Grant SF. The genetics of human obesity. Ann N Y Acad Sci. 2013;1281(1):178.

Kaila B, Raman M. Obesity: a review of pathogenesis and management strategies. Can J Gastroenterol Hepatol. 2008;22(1):61-8.

Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci. 2016;130(12):943-86.

Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr. 2008;87(2):398-404.

Farooqi IS, O'Rahilly S. Monogenic obesity in humans. Annu Rev Med. 2005;56:443-58.

Farooqi IS, O'Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27(7):710-8.

Fairbrother U, Kidd E, Malagamuwa T, Walley A. Genetics of severe obesity. Curr Diab Rep. 2018;18(10):85.

Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Rev Endocrinol. 2008;4(11):619.

Festa A, D'Agostino Jr, Williams K, Karter AJ, Mayer-Davis EJ, Tracy RP, et al. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord. 2001;25(10):1407.

Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract. 2005;69(1):29-35.

Murdaca G, Contini P, Negrini S, Ciprandi G, Puppo F. Immunoregulatory role of HLA-G in allergic diseases. J Immunol Res. 2016;2016.

Yie SM, Li LH, Li YM, Librach C. HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia. Am J Obstet Gynecol. 2004;191:525–9.

Peng B, Zhang L, Xing AY, Hu M, Liu SY. The expression of human leukocyte antigen G and E on human first trimester placenta and its relationship with recurrent spontaneous abortion. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008;39:976–9.

Alegre E, Rizzo R, Bortolotti D, Fernandez-Landázuri S, Fainardi E, González A. Some basic aspects of HLA-G biology. J Immunol Res. 2014;2014.

Donadi EA, Castelli EC, Arnaiz-Villena A, Roger M, Rey D, Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell Mol Life Sci. 2011;68(3):369-5.

Poomarimuthu M, Elango S, Soundrapandian S, Mariakuttikan J. HLA-G 3′ UTR gene polymorphisms and rheumatic heart disease: a familial study among South Indian population. Pediatr Rheumatol. 2017;15(1):10.

García-González IJ, Valle Y, Rivas F, Figuera-Villanueva LE, Muñoz-Valle JF, Flores-Salinas HE, et al. The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute coronary syndrome and type 2 diabetes mellitus. Biomed Res Int. 2014;2014.

Brenol CV, Veit TD, Chies JAB, Xavier RM. The role of the HLA-G gene and molecule on the clinical expression of rheumatologic diseases. Rev Bras Reumatol. 2012;52(1):82-91.

Shankarkumar U, Shankarkumar A, Chedda Z, Ghosh K. Role of 14-bp deletion/insertion polymorphism in exon 8 of the HLA-G gene in recurrent spontaneous abortion patients. J Hum Reprod Sci. 2011;4(3):143.

Boiocchi C, Bozzini S, Zorzetto M, Pelissero G, Cuccia M, Falcone C. Association between two polymorphisms in the HLA-G gene and angiographic coronary artery disease. Mol Med Rep. 2012;5(5):1141-5.

Dardano A, Rizzo R, Polini A, Stignani M, Tognini S, Pasqualetti G, et al. Soluble human leukocyte antigen-g and its insertion/deletion polymorphism in papillary thyroid carcinoma: novel potential biomarkers of disease? J Clin Endocrinol Metab. 2012;97(11):4080-6.

Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: pathophysiology and management. J Am Coll Cardiol. 2018;71(1):69-84.

Chesi A, Grant SF. The genetics of pediatric obesity. Trends Endocrinol Metab. 2015;26(12):711-21.

Kelishadi R, Roufarshbaf M, Soheili S, Payghambarzadeh F, Masjedi M. Association of childhood obesity and the immune system: a systematic review of reviews. Child Obes. 2017;13(4):332-46.

Dias FC, Castelli EC, Collares CV, Moreau P, Donadi EA. The role of HLA-G molecule and HLA-G gene polymorphisms in tumors, viral hepatitis, and parasitic diseases. Front Immunol. 2015;6:9.

Eskandari-Nasab E, Hashemi M, Hasani SS, Omrani M, Taheri M, Mashhadi MA. Association between HLA-G 3'UTR 14-bp ins/del polymorphism and susceptibility to breast cancer. Cancer Biomark. 2013;13(4):253-9.

Jiang Y, Lu J, Wu YE, Zhao X, Li L. Genetic variation in the HLA-G 3′ UTR 14–bp insertion/deletion and the associated cancer risk: evidence from 25 case–control studies. Biosci Rep. 2019;39(5).

Hashemi M, Sandoughi M, Fazeli SA, Bahari G, Rezaei M, Zakeri Z. Evaluation of HLA-G 14 bp Ins/Del and+ 3142G> C polymorphism with susceptibility and early disease activity in rheumatoid arthritis. Adv Med. 2016;2016.

Marzuillo P, Bellini G, Punzo F, Sessa AD, Guarino S, Umano GR, et al. Association between 14 bp insertion/deletion HLA‐G functional polymorphism and insulin resistance in a cohort of Italian children with obesity. Pediatr Diabetes. 2018;19(8):1357-61.

Ge YZ, Ge Q, Li H, Shi GM, Xu X, Xu LW, et al. Association between human leukocyte antigen-G 14-bp insertion/deletion polymorphism and cancer risk: a meta-analysis and systematic review. Hum Immunol. 2014;75(8):827-32.

Chen Y, Gao XJ, Deng Y, Zhang H. Relationship between HLA-G gene polymorphism and the susceptibility of esophageal cancer in Kazakh and Han nationality in Xinjiang. Biomarkers. 2012;17(1):9-15.

Castelli EC, Veiga-Castelli LC, Yaghi L, Moreau P, Donadi EA. Transcriptional and posttranscriptional regulations of the HLA-G gene. J Immunol Res. 2014;2014.

Durmanova V, Drobny J, Shawkatova I, Dlhopolcek J, Bucova M. Analysis of HLA-G gene polymorphisms in Slovak women with pre-eclampsia. Bratisl Lek Listy. 2017;118(9):517-22.

Monti M, Lupoli R, Fernandez LMS, Cirillo F, Di Minno MND. Association of human leukocyte antigen-G 14 bp polymorphism with recurrent pregnancy loss in European countries: a meta-analysis of literature studies. Fertil Steril. 2019;112(3):577-85.






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Mohammad A, Mıhçıoğlu D, Gerçeker F, Aksoy B. Investigation of the association between HLA-G polymorphisms and obesity. J Surg Med [Internet]. 2022 Apr. 1 [cited 2024 Jul. 15];6(4):436-9. Available from: