Top

Journal of Translational Medicine

Published in:

Open Access 01-12-2018 | Research

Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case–control study

Authors: Maryam Dendana, Wael Bahia, Ramzi R. Finan, Mariam Al-Mutawa, Wassim Y. Almawi

Published in: Journal of Translational Medicine | Issue 1/2018

Abstract

Background

This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity.

Methods

Retrospective case–control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR.

Results

Of the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively.

Conclusion

This is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies.

Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013;99:63.CrossRef

Tang AW, Quenby S. Recent thoughts on management and prevention of recurrent early pregnancy loss. Curr Opin Obstet Gynecol. 2010;22:446–51.CrossRefPubMed

Lashen H, Fear K, Sturdee DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod. 2004;19:1644–6.CrossRefPubMed

Sugiura-Ogasawara M. Recurrent pregnancy loss and obesity. Best Pract Res Clin Obstet Gynaecol. 2015;29:489–97.CrossRefPubMed

Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med. 2015;5(3):a023119.CrossRefPubMedPubMedCentral

Mathew H, Castracane VD, Mantzoros C. Adipose tissue and reproductive health. Metabolism. 2017. https://doi.org/10.1016/j.metabol.2017.11.006.PubMed

Ingram KH, Hunter GR, James JF, Gower BA. Central fat accretion and insulin sensitivity: differential relationships in parous and nulliparous women. Int J Obes (Lond). 2017;41:1214–7.CrossRef

Bao W, Baecker A, Song Y, Kiely M, Liu S, Zhang C. Adipokine levels during the first or early second trimester of pregnancy and subsequent risk of gestational diabetes mellitus: a systematic review. Metabolism. 2015;64:756–64.CrossRefPubMedPubMedCentral

Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism. 2015;64:131–45.CrossRefPubMed

10.

Baviera G, Corrado F, Dugo C, Cannata ML, Russo S, Rosario D. Midtrimester amniotic fluid adiponectin in normal pregnancy. Clin Chem. 2007;53:1723–4.CrossRefPubMed

11.

Mazaki-Tovi S, Romero R, Vaisbuch E, et al. Adiponectin in amniotic fluid in normal pregnancy, spontaneous labor at term, and preterm labor: a novel association with intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2010;23:120–30.CrossRefPubMedPubMedCentral

12.

Angelidis G, Dafopoulos K, Messini CI, et al. The emerging roles of adiponectin in female reproductive system associated disorders and pregnancy. Reprod Sci. 2013;20:872–81.CrossRefPubMed

13.

Palin M-C, Bourdignon VV, Murphy BD. Adiponectin and the control of female reproductive functions. Vitam Horm. 2012;90:239–87.CrossRefPubMed

14.

Cortelazzi D, Corbetta S, Ronzoni S, et al. Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies. Clin Endocrinol (Oxf). 2007;66:447–53.CrossRef

15.

Kawwass JF, Summer R, Kallen CB. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review. Mol Hum Reprod. 2015;21:617–32.CrossRefPubMedPubMedCentral

16.

Verma PK, Prakash S, Parveen F, Faridi RM, Agrawal S. Genetic association of adipokine and UCP2 polymorphism with recurrent miscarriage among non-obese women. Reprod Bio Med Online. 2012;25:527–35.CrossRef

17.

Heid IM, Wagner SA, Gohlke H, et al. Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1727 healthy Caucasians. Diabetes. 2006;55:375–84.CrossRefPubMed

18.

Chung HK, Chae JS, Hyun YJ, et al. Influence of adiponectin gene polymorphisms on adiponectin level and insulin resistance index in response to dietary intervention in overweight-obese patients with impaired fasting glucose or newly diagnosed type 2 diabetes. Diabetes Care. 2009;32:552–8.CrossRefPubMedPubMedCentral

19.

Menzaghi C, Ercolino T, Salvemini L, et al. Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13. Physiol Genom. 2004;19:170–4.CrossRef

20.

Beltcheva O, Boyadzhieva M, Angelova O, Mitev V, Kaneva R, Atanasova I. The rs266729 single-nucleotide polymorphism in the adiponectin gene shows association with gestational diabetes. Arch Gynecol Obstet. 2014;289:743–8.CrossRefPubMed

21.

Machado JS, Cavalli RC, Sandrim VC, et al. Study of polymorphisms of the adiponectin gene in women with gestational hypertension and preeclampsia. Pregnancy Hypertens. 2012;2(3):241.CrossRefPubMed

22.

Pawlik A, Teler J, Maciejewska A, Sawczuk M, Safranow K, Dziedziejko V. Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus. J Assist Reprod Genet. 2017;34:511–6.CrossRefPubMed

23.

Park JW, Park J, Jee SH. ADIPOQ gene variants associated with susceptibility to obesity and low serum adiponectin levels in healthy Koreans. Epidemiol Health. 2011;33:e201100325.

24.

Saarela T, Hiltunen M, Helisalmi S, Heinonen S, Laakso M. Adiponectin gene haplotype is associated with preeclampsia. Genet Test. 2006;10:35–9.CrossRefPubMed

25.

Peters KE, Beilby J, Cadby G, Warrington NM, Bruce DG, Davis WA, Davis TM, Wiltshire S, Knuiman M, McQuillan BM, Palmer LJ, Thompson PL, Hung J. A comprehensive investigation of variants in genes encoding adiponectin(ADIPOQ) and its receptors (ADIPOR1/R2), and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome. BMC Med Genet. 2013;14:15.CrossRefPubMedPubMedCentral

26.

Ranjzad F, Mahmoudi T, Irani Shemirani A, Mahban A, Nikzamir A, Vahedi M, Ashrafi M, Gourabi H. A common variant in the adiponectin gene and polycystic ovary syndrome risk. Mol Biol Rep. 2012;39:2313–9.CrossRefPubMed

27.

Wang Y, Liu RX, Liu H. Association of adiponectin gene polymorphisms with hypertensive disorder complicating pregnancy and disorders of lipid metabolism. Genet Mol Res. 2015;14:15213–23.CrossRefPubMed

28.

Vasseur F, Helbecque N, Lobbens S, et al. Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity. Diabetologia. 2005;48:892–9.CrossRefPubMed

29.

Zhang D, Ma J, Brismar K, Efendic S, Gu HF. A single nucleotide polymorphism alters the sequence of SP1 binding site in the adiponectin promoter region and is associated with diabetic nephropathy among type 1 diabetic patients in the genetics of kidneys in diabetes study. J Diab Compl. 2009;23:265–72.CrossRef

30.

Liang C, Yawei X, Qinwan W, Jingying Z, Aihong M, Yanqing C. Association of ADIPOQ single-nucleotide polymorphisms and smoking interaction with the risk of coronary heart disease in Chinese Han population. Clin Exp Hypertens. 2017;39:748–53.CrossRefPubMed

31.

Cohen SS, Gammon MD, North KE, et al. ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms in relation to serum adiponectin levels and BMI in black and white women. Obesity. 2011;19:2053–62.CrossRefPubMedPubMedCentral

32.

Siitonen N, Pulkkinen L, Lindström J, et al. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the finnish diabetes prevention study. BMC Med Genet. 2011;12:5.CrossRefPubMedPubMedCentral

33.

Mtiraoui N, Ezzidi I, Turki A, Chaieb A, Mahjoub T, Almawi WY. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012;97:290–7.CrossRefPubMed

34.

Richardson DK, Schneider J, Fourcaudot MJ, et al. Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans. Diabetologia. 2006;49:2317–28.CrossRefPubMed

35.

Ye Y, Pu D, Liu J, Li F, Cui Y, Wu J. Adiponectin gene polymorphisms may not be associated with idiopathic premature ovarian failure. Gene. 2013;518:262–6.CrossRefPubMed

36.

Zhang W, Wei D, Sun X, Li J, Yu X. Family-based analysis of adiponectin gene polymorphisms in Chinese Han polycystic ovary syndrome. Fertil Steril. 2014;101:1419–23.CrossRefPubMed

37.

Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med. 2011;29:507–13.CrossRefPubMed

38.

Khandouzi M, Deka M. The role of adiponectin in human pregnancy. Int J Res Engin Technol. 2014;2:93–100.

39.

Cikos S, Burkus J, Bukovska A, Fabian D, Rehak P, Koppel J. Expression of adiponectin receptors and effects of adiponectin isoforms in mouse pre-implantation embryos. Hum Reprod. 2010;25:2247–55.CrossRefPubMed

40.

Kim ST, Marquard K, Stephens S, Louden E, Allsworth J, Moley KH. Adiponectin and adiponectin receptors in the mouse preimplantation embryo and uterus. Hum Reprod. 2011;26:82–95.CrossRefPubMed

41.

Richards JS, Liu Z, Kawai T, et al. Adiponectin and its receptors modulate granulosa cell and cumulus cell functions, fertility and early embryo development in the mouse and human. Fertil Steril. 2012;98:471–9.CrossRefPubMedPubMedCentral

42.

Hivert MF, Scholtens DM, Allard C, et al. Genetic determinants of adiponectin regulation revealed by pregnancy. Obesity. 2017;25:935–44.CrossRefPubMedPubMedCentral

Title: Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case–control study
Authors: Maryam Dendana
Wael Bahia
Ramzi R. Finan
Mariam Al-Mutawa
Wassim Y. Almawi
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-018-1453-3

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case–control study

Abstract

Background

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

Roles of airway smooth muscle dysfunction in chronic obstructive pulmonary disease

Integrated analysis of dysregulated long non-coding RNAs/microRNAs/mRNAs in metastasis of lung adenocarcinoma

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons

Comprehensive and integrative analysis identifies microRNA-106 as a novel non-invasive biomarker for detection of gastric cancer

Adolescent mental health education InSciEd Out: a case study of an alternative middle school population

Improved CD4 T cell profile in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page