Association between LXR-α and ABCA1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus in a Chinese Han Population.

Peng Liu,Xinping Qiu,Meihua Yan,Ping Li,Liang Ma,Tingting Zhao,Xuefeng Zhou,Hailing Zhao,Haojun Zhang,Zhengri Shen,Linlin Zhang

doi:10.1155/2020/8721536

Peng Liu, Xinping Qiu + Show 9 more

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https://doi.org/10.1155/2020/8721536

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Journal: Journal of diabetes research	Publication Date: Dec 22, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: China-Japan Friendship Hospital

Abstract

We designed a case-control study and selected LXR-α rs7120118 C>T and ABCA1 rs2230806 A>G polymorphisms to determine the correlation between these polymorphisms and diabetic kidney disease (DKD) susceptibility in a Chinese Han population. Three hundred DKD patients and 346 type 2 diabetes mellitus (DM) patients without kidney disease were recruited. Our results showed that rs7120118 was associated with DKD (genotype, P = .027; allele, P < .011). rs7120118 was associated with a higher risk of DKD under a dominant model adjustment by age and sex (P = .015) and an additive model (P = .040); rs2230806 was associated with a higher risk of DKD under an recessive model (P < .03); the combined effect of rs7120118 CC+rs2230806 GG genotype showed an association of DKD adjustment for age and sex (P = .009). In subgroup analysis of patients without hypercholesterolemia, the rs2230806 genotype frequencies were different between the two groups (P = .042). rs2230806 was associated with increased risk of DKD under a recessive model adjustment for age and sex (P = .013) and an additive model (P = .031). Our results suggest that LXR-α rs7120118 is significantly associated with a higher risk of DKD, and ABCA1 rs2230806 is significantly associated with a higher risk of DKD without hypercholesterolemia in Chinese Han individuals.

Highlights

Diabetic kidney disease (DKD), a devastating complication of diabetes mellitus (DM), is the most common cause of end-stage renal disease (ESRD) and renal failure in the world [1]
All clinical characteristics including body mass index (BMI), history of hypertension, blood pressure, serum creatinine (Scr), total cholesterol (TC), TG, and low-density lipoprotein cholesterol (LDL-C) were found to be elevated in DKD patients as compared with controls (Table 1)
When the rs7120118 CC homozygote genotype was used as the reference, the TC and TT genotypes were associated with a decreased risk of DKD (TC versus CC: odds ratio (OR), 0.719; 95% CI 0.522-0.990; TT versus CC: OR, 0.460; 95% CI 0.224-0.946; trend P = :043) in the additive model

Summary

Introduction

Diabetic kidney disease (DKD), a devastating complication of diabetes mellitus (DM), is the most common cause of end-stage renal disease (ESRD) and renal failure in the world [1]. Genetic factors are directly related to the initiation and progression of DKD, including aggregation in families and variable incidence rates between different races [3, 4]. Lipid metabolism disorders are an important factor that leads to DKD progression [6]. Physiologic processes that are affected by LXRs include inflammation, metabolism and homeostasis of lipids, and cholesterol homeostasis [8]. Multiple common single-nucleotide polymorphisms (SNPs) in LXR-α are associated with a higher risk of coronary heart disease and hemodialysis [10, 11]. Patients carrying the allele T (i.e., CT or TT) at rs7120118 have low Journal of Diabetes Research serum lipid levels, while those with the C allele have high serum lipid levels in coronary heart disease and hemodialysis [10, 11]. It has been shown that rs7120118 is associated with the expression of LXR-α [12]

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