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Journal of Diabetes & Metabolic Disorders
Published in: Journal of Diabetes & Metabolic Disorders 1/2021

01-06-2021 | Diabetes | Research article

Significant association of LXRβ (NR1H2) polymorphisms (rs28514894, rs2303044) with type 2 diabetes mellitus and laboratory characteristics

Authors: Mohammad Bagher Sadeghi, Alireza Nakhaee, Ramin Saravani, Saman Sargazi

Published in: Journal of Diabetes & Metabolic Disorders | Issue 1/2021

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Abstract

Purpose

To investigate if single-nucleotide polymorphisms (SNPs) in the NR1H2 gene encoding LXRβ contribute to the development of type-2 diabetes mellitus (T2DM) and whether genotypes of two NR1H2 polymorphisms, rs28514894 and rs2303044, are associated with laboratory characteristics of T2DM patients.

Method

A total of 900 subjects (450 T2DM cases and 450 healthy subjects) of Iranian ancestry were genotyped for NR1H2 polymorphisms via ARMS-PCR and PCR-RFLP techniques.

Result

Our findings showed a significant correlation between both polymorphisms and increased risk of T2DM. The haplotype analysis showed an association between the C A haplotype with enhanced risk of T2DM. In T2DM patients, the mean level of HbA1C and BUN significantly differed among carriers of CC and TT genotypes of the rs28514894 polymorphism (P = 0.05 and P < 0.0001, respectively); while in the control group, no significant difference was noticed between subjects with these genotypes. The mean BUN levels also significantly differed among carriers of TC and TT genotypes of this variant in T2DM patients (P = 0.01) and controls (P = 0.04). As for rs2303044 polymorphism, only the mean BUN level significantly differed between GA and GG carriers in T2DM patients (P = 0.006). Compared with CT and TT genotypes, the CC genotype of rs28514894 polymorphism was more frequent in overweight T2DM patients ( 25 < body mass index < 30).

Conclusions

The present research provided the first documents of the correlation of NR1H2 rs28514894 and rs2303044 polymorphisms with susceptibility to T2DM. Replicated case-control studies on larger populations are needed to validate these findings.
Literature
1.
Cersosimo E, Triplitt C, Solis-Herrera C, Mandarino LJ, DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Endotext [Internet]. Portland: MDText. com, Inc.; 2018.
2.
Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107.PubMedPubMedCentralCrossRef
3.
Golozar A, Khalili D, Etemadi A, Poustchi H, Fazeltabar A, Hosseini F, et al. White rice intake and incidence of type-2 diabetes: analysis of two prospective cohort studies from Iran. BMC Public Health. 2017;17(1):133.PubMedPubMedCentralCrossRef
4.
Li Y-Y, Wang H, Yang X-X, Wu J-J, Geng H-Y, Kim HJ, et al. LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: a meta-analysis of 3,367 subjects. Oncotarget. 2017;8(37):61927.PubMedPubMedCentralCrossRef
5.
Schlienger J-L. Type 2 diabetes complications. Press Med (Paris, France: 1983). 2013;42(5):839–48.
6.
Bigagli E, Lodovici M. Circulating oxidative stress biomarkers in clinical studies on type 2 diabetes and its complications. Oxid Med Cell Longev. 2019;2019:5953685.PubMedPubMedCentralCrossRef
7.
Mambiya M, Shang M, Wang Y, Li Q, Liu S, Yang L, et al. The Play of genes and non-genetic factors on type 2 diabetes. Front Public Health. 2019;7:349.
8.
Bardini G, Rotella CM, Giannini S. Dyslipidemia and diabetes: reciprocal impact of impaired lipid metabolism and Beta-cell dysfunction on micro-and macrovascular complications. Rev Diabet Stud. 2012;9(2–3):82.PubMedPubMedCentralCrossRef
9.
10.
11.
12.
Ulven SM, Dalen KT, Gustafsson J-Å, Nebb HI. LXR is crucial in lipid metabolism. Prostaglandins Leukot Essent Fatty Acids. 2005;73(1):59–63.PubMedCrossRef
13.
Pascual-García M, Valledor AF. Biological roles of liver X receptors in immune cells. Arch Immunol Ther Exp. 2012;60(4):235–49.CrossRef
14.
Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, et al. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci. 2003;100(9):5419–24.PubMedPubMedCentralCrossRef
15.
Beaven SW, Matveyenko A, Wroblewski K, Chao L, Wilpitz D, Hsu TW, et al. Reciprocal regulation of hepatic and adipose lipogenesis by liver X receptors in obesity and insulin resistance. Cell Metabol. 2013;18(1):106–17.CrossRef
16.
Korach-André M, Parini P, Larsson L, Arner A, Steffensen KR, Gustafsson J-Å. Separate and overlapping metabolic functions of LXRα and LXRβ in C57Bl/6 female mice. Am J Physiol Endocrinol Metab. 2010;298(2):E167–178.PubMedCrossRef
17.
Gabbi C, Kong X, Suzuki H, Kim H-J, Gao M, Jia X, et al. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β. Proc Natl Acad Sci. 2012;109(8):3030–4.PubMedPubMedCentralCrossRef
18.
Meng Z, Yin Y, Lv J, Sha M, Lin Y, Gao L, et al. Aberrant activation of liver X receptors impairs pancreatic beta cell function through upregulation of sterol regulatory element-binding protein 1c in mouse islets and rodent cell lines. Diabetologia. 2012;55(6):1733–44.PubMedCrossRef
19.
Heidari Z, Harati-Sadegh M, Arian A, Maruei-Milan R, Salimi S. The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features. IUBMB Life. 2020;72(5):922–30.PubMedCrossRef
20.
Mohammadpour-Gharehbagh A, Jahantigh D, Saravani M, Harati‐Sadegh M, Maruie‐Milan R, Teimoori B, et al. Impact of HOTAIR variants on preeclampsia susceptibility based on blood and placenta and in silico analysis. IUBMB Life. 2019;71(9):1367–81.PubMedCrossRef
21.
Salimi S, Harati-Sadegh M, Eskandari M, Heidari Z. The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma. IUBMB Life. 2020;72(5):1045–53.PubMedCrossRef
22.
Mouzat K, Mercier E, Polge A, Evrard A, Baron S, Balducchi J-P, et al. A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia. BMC Med Genet. 2011;12(1):145.PubMedPubMedCentralCrossRef
23.
Rooki H, Ghayour-Mobarhan M, Haerian M-s, Ebrahimi M, Azimzadeh P, Heidari-Bakavoli A, et al. Lack of association between LXRα and LXRβ gene polymorphisms and prevalence of metabolic syndrome: A case–control study of an Iranian population. Gene. 2013;532(2):288–93.PubMedCrossRef
24.
Legry V, Cottel D, Ferrières J, Chinetti G, Deroide T, Staels B, et al. Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations. Int J Obes. 2008;32(3):421–8.CrossRef
25.
Solaas K, Legry V, Retterstol K, Berg PR, Holven KB, Ferrières J, et al. Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe). BMC Med Genet. 2010;11(1):144.PubMedPubMedCentralCrossRef
26.
Buroker NE. Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness. World J Hematol. 2016;5(4):75–87.CrossRef
27.
28.
Caprio S. Development of type 2 diabetes mellitus in the obese adolescent: a growing challenge. Endocr Pract. 2012;18(5):791–5.PubMedCrossRef
29.
30.
Sargazi S, Nia MH, Sargazi FM, Sheervalilou R, Saravani R, Mirinejad S. SNPs in the 3′-untranslated region of SLC30A8 confer risk of type 2 diabetes mellitus in a south-east Iranian population: Evidences from case-control and bioinformatics studies. J Diabetes Metab Disord. 2020;1–10.
31.
Juttada U, Kumpatla S, Parveen R, Viswanathan V. TCF7L2 polymorphism a prominent marker among subjects with Type-2-Diabetes with a positive family history of diabetes. Int J Biol Macromol. 2020;159:402–5.PubMedCrossRef
32.
Green CD, Jump DB, Olson LK. Elevated insulin secretion from liver X receptor-activated pancreatic β-cells involves increased de novo lipid synthesis and triacylglyceride turnover. Endocrinology. 2009;150(6):2637–45.PubMedPubMedCentralCrossRef
33.
Maczewsky J, Sikimic J, Bauer C, Krippeit-Drews P, Wolke C, Lendeckel U, et al. The LXR ligand T0901317 acutely inhibits insulin secretion by affecting mitochondrial metabolism. Endocrinology. 2017;158(7):2145–54.PubMedCrossRef
34.
Meng Z, Nie J, Ling J, Sun J, Zhu Y, Gao L, et al. Activation of liver X receptors inhibits pancreatic islet beta cell proliferation through cell cycle arrest. Diabetologia. 2009;52(1):125.PubMedCrossRef
35.
Choe SS, Choi AH, Lee J-W, Kim KH, Chung J-J, Park J, et al. Chronic activation of liver X receptor induces β-cell apoptosis through hyperactivation of lipogenesis: liver X receptor–mediated lipotoxicity in pancreatic β-cells. Diabetes. 2007;56(6):1534–43.PubMedCrossRef
36.
Johnston AD, Simões-Pires CA, Thompson TV, Suzuki M, Greally JM. Functional genetic variants can mediate their regulatory effects through alteration of transcription factor binding. Nat Commun. 2019;10(1):1–16.CrossRef
37.
Moyer RA, Wang D, Papp AC, Smith RM, Duque L, Mash DC, et al. Intronic polymorphisms affecting alternative splicing of human dopamine D2 receptor are associated with cocaine abuse. Neuropsychopharmacology. 2011;36(4):753–62.PubMedCrossRef
38.
Bufalo N, Dos Santos R, Marcello M, Piai R, Secolin R, Romaldini J, et al. TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves’ disease and Graves’ ophthalmopathy. J Endocrinol Invest. 2015;38(5):555–61.PubMedCrossRef
39.
Greenwood TA, Kelsoe JR. Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics. 2003;82(5):511–20.PubMedCrossRef
40.
Fukae A, Ikeda S, Inoue M, Tachibana T, Inamine T, Kondo S, et al. The evidence of polymorphisms of the liver X receptor gene as a DNA-based biomarker for susceptibility to coronary artery disease in a Japanese population. Acta Med Nagasaki. 2011;55(2):69–76.
41.
Ketterer C, Müssig K, Machicao F, Stefan N, Fritsche A, Häring H-U, et al. Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes. J Mol Med. 2011;89(1):75–81.PubMedCrossRef
42.
Dahlman I, Nilsson M, Gu HF, Lecoeur C, Efendic S, Östenson CG, et al. Functional and genetic analysis in type 2 diabetes of liver X receptor alleles–a cohort study. BMC Med Genet. 2009;10(1):27.PubMedPubMedCentralCrossRef
43.
Han M, Liang L, Liu L-r, Yue J, Zhao Y-l. Xiao H-p. Liver X receptor gene polymorphisms in tuberculosis: effect on susceptibility. PLoS One. 2014;9(5):e95954.PubMedPubMedCentralCrossRef
44.
Oliveira FFd, Chen ES, Smith MC, Bertolucci PH. Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer’s disease dementia. Braz J Psychiatry. 2017;39(2):95–103.PubMedPubMedCentralCrossRef
45.
Mehrad-Majd H, Ghayour-Mobarhan M, Zali M-R. Genetic association of liver X receptor beta rs2695121 polymorphism with obesity-related traits in a northeastern Iranian population. Electron Physician. 2018;10(1):6249.PubMedPubMedCentralCrossRef
46.
Engwa GA, Nwalo FN, Chikezie CC, Onyia CO, Ojo OO, Mbacham WF, et al. Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population. BMC Med Genet. 2018;19(1):1–7.CrossRef
47.
Li J, Wei J, Xu P, Yan M, Li J, Chen Z, et al. Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population. Oncotarget. 2016;7(51):85464.PubMedPubMedCentralCrossRef
48.
49.
Metadata
Title
Significant association of LXRβ (NR1H2) polymorphisms (rs28514894, rs2303044) with type 2 diabetes mellitus and laboratory characteristics
Authors
Mohammad Bagher Sadeghi
Alireza Nakhaee
Ramin Saravani
Saman Sargazi
Publication date
01-06-2021
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 1/2021
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-021-00740-3

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