Genetic factors associated with dyslipidemia, T2DM and DKD: a cross-sectional study on FXR gene polymorphisms

Xushan Lan , Chenguang Wu , Zhengri Shen , Rui Zhang , Chengqian Yin , Jinfeng Qi , Lifan Wang , Peng Liu , Ping Li

Journal of Translational Genetics and Genomics ›› 2025, Vol. 9 ›› Issue (3) : 219 -30.

PDF
Journal of Translational Genetics and Genomics ›› 2025, Vol. 9 ›› Issue (3) :219 -30. DOI: 10.20517/jtgg.2025.62
review-article

Genetic factors associated with dyslipidemia, T2DM and DKD: a cross-sectional study on FXR gene polymorphisms

Author information +
History +
PDF

Abstract

Aim: Genetic factors play a critical role in the development and progression of type 2 diabetes (T2DM) and diabetic kidney disease (DKD). Recent studies have reported associations between single nucleotide polymorphisms (SNPs) in the farnesoid X receptor (FXR) gene and the risk of T2DM and DKD. Dyslipidemia is increasingly recognized as a risk factor for DKD in patients with T2DM. This study aimed to investigate the potential genetic contribution of FXR gene SNPs rs11110390 and rs4764980 to susceptibility to T2DM and DKD in a Chinese population.

Methods: This cross-sectional study included 168 patients with dyslipidemia and diabetes, comprising 90 T2DM patients and 78 DKD patients, along with 159 healthy controls. Genotyping of FXR SNPs rs11110390 and rs4764980 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Associations between FXR polymorphisms and disease risk were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Regression analysis revealed that neither the genotypes nor the alleles of FXR rs11110390 and rs4764980 were significantly associated with T2DM risk. In contrast, the rs4764980 GA genotype was significantly associated with an increased risk of DKD (OR = 2.985; 95%CI = 1.412-6.312; P = 0.004).

Conclusion: The FXR rs4764980 GA genotype may confer increased susceptibility to DKD in the Chinese population. However, no significant associations were observed between rs11110390 or rs4764980 and T2DM risk or overall DKD risk.

Keywords

Diabetic kidney disease / FXR gene / polymorphism / type 2 diabetes / dyslipidemia

Cite this article

Download citation ▾
Xushan Lan, Chenguang Wu, Zhengri Shen, Rui Zhang, Chengqian Yin, Jinfeng Qi, Lifan Wang, Peng Liu, Ping Li. Genetic factors associated with dyslipidemia, T2DM and DKD: a cross-sectional study on FXR gene polymorphisms. Journal of Translational Genetics and Genomics, 2025, 9(3): 219-30 DOI:10.20517/jtgg.2025.62

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

ZengQ,ZengQ,WeiY.Association between insulin-like growth factor-1 rs35767 polymorphism and type 2 diabetes mellitus susceptibility: a meta-analysis.Front Genet2021;12:774489 PMCID:PMC8646032

[2]

KwakSH.Recent progress in genetic and epigenetic research on type 2 diabetes.Exp Mol Med2016;48:e220 PMCID:PMC4892885

[3]

WangJ,WuC,LiuP.Exploring potential targets for natural product therapy of DN: the role of SUMOylation.Front Pharmacol2024;15:1432724

[4]

ZhouY,WangX,LiuQ.Insights into the functional mechanism of diabetic kidney disease treatment with sinensetin based on network pharmacology and molecular docking.Integr Med Nephrol Androl2023;10:e00033

[5]

ZhouS,XuR.Statin initiation and risk of incident kidney disease in patients with diabetes.Can Med Assoc J2023;195:E729-38 PMCID:PMC10228577

[6]

DengY,XingJ.The role of natural products in improving lipid metabolism disorder-induced mitochondrial dysfunction of diabetic kidney disease.Front Physiol2025;16:1624077 PMCID:PMC12234459

[7]

LuanZL,MingWH,GuanYF.Nuclear receptors in renal health and disease.EBioMedicine2022;76:103855 PMCID:PMC8819107

[8]

ZhouH.Bile acids are nutrient signaling hormones.Steroids2014;86:62-8 PMCID:PMC4073476

[9]

JiangT,ScherzerP.Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy.Diabetes2007;56:2485-93

[10]

LiuP,WangC,QiuX.Tangshen formula ameliorates renal fibrosis of diabetic kidney disease through regulating the FXR/vimentin/α-SMA pathway.J Beijing University Traditional Chinese Med2022;45:1196-204

[11]

MaL,KongX.Association of EPHX2 R287Q polymorphism with diabetic nephropathy in Chinese type 2 diabetic patients.J Diabetes Res2018;2786470 PMCID:PMC5832179

[12]

ZhaoH,YanM.Association between MYH9 and APOL1 gene polymorphisms and the risk of diabetic kidney disease in patients with type 2 diabetes in a Chinese Han population.J Diabetes Res2018;5068578 PMCID:PMC5971321

[13]

GrantSF,ReynisdottirI.Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.Nat Genet2006;38:320-3

[14]

ImamuraM.Genetics of type 2 diabetes: the GWAS era and future perspectives [Review].Endocr J2011;58:723-39

[15]

LyssenkoV,MarchettiP.Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.J Clin Invest2007;117:2155-63

[16]

MahajanA,WillemsSM.Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet2018;50:559-71 PMCID:PMC5898373

[17]

ZegginiE,SaxenaR.Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.Nat Genet2008;40:638-45

[18]

AltshulerD,KlannemarkM.The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.Nat Genet2000;26:76-80

[19]

FraylingTM,WeedonMN.A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.Science2007;316:889-94

[20]

HuM,TamLS,TomlinsonB.The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin.J Lipid Res2012;53:1384-9 PMCID:PMC3371250

[21]

WangXX,LuoY.FXR/TGR5 dual agonist prevents progression of nephropathy in diabetes and obesity.J Am Soc Nephrol2018;29:118-37

[22]

HeniM,KettererC.Genetic variation in NR1H4 encoding the bile acid receptor FXR determines fasting glucose and free fatty acid levels in humans.J Clin Endocrinol Metab2013;98:E1224-9

[23]

FangY,ZhengQ.Role of bile acid receptors in the development and function of diabetic nephropathy.Kidney Int Rep2024;9:3116-33 PMCID:PMC11551060

[24]

WangJ,KongR.Association between globulin and diabetic nephropathy in Type2 diabetes mellitus patients: a cross-sectional study.Front Endocrinol2022;13:890273 PMCID:PMC9311329

[25]

HuY.[Blood lipid indicators and different clinical classifications of dyslipidemia and diabetic kidney disease: correlation and predictive value].Sichuan Da Xue Xue Bao Yi Xue Ban2023;54:1013-8 PMCID:PMC10579073

[26]

TralongoAC,ProserpioI,CampiottiL.Body mass index (BMI) influence on Cetuximab-induced antibody-dependent cellular cytotoxicity in advanced colon cancer.Intern Emerg Med2023;18:297-303 PMCID:PMC9883300

[27]

BeaneyT,KiruG.May measurement month 2022: results from the global blood pressure screening campaign.BMJ Glob Health2024;9:e016557 PMCID:PMC11624700

[28]

DelanayeP,PottelH.New and old GFR equations: a European perspective.Clin Kidney J2023;16:1375-83 PMCID:PMC10469124

[29]

DelgadoC,CrewsDC.A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease.Am J Kidney Dis2022;79:268-88.e1

AI Summary AI Mindmap
PDF

41

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/