Investigation of the Correlation Between the Polymorphism/Expression Level of RANTES and Its Receptor CCR5 Gene Promoter and Type 2 Diabetes Mellitus

Jie Chen; Weichang Guo; Hejia Yin; Liju Ma; Shaoyou Li; Huifang Li

doi:10.2147/DMSO.S398264

Investigation of the Correlation Between the Polymorphism/Expression Level of RANTES and Its Receptor CCR5 Gene Promoter and Type 2 Diabetes Mellitus

Diabetes Metab Syndr Obes. 2023 Jan 24:16:213-223. doi: 10.2147/DMSO.S398264. eCollection 2023.

Authors

Jie Chen^#¹, Weichang Guo^#², Hejia Yin¹, Liju Ma³, Shaoyou Li⁴, Huifang Li¹

Affiliations

¹ Department of Diabetes, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People's Republic of China.
² Department of Physical Education, Kunming Medical University, Kunming, 650032, People's Republic of China.
³ Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People's Republic of China.
⁴ Department of The Scientific Research Laboratory Center, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People's Republic of China.

^# Contributed equally.

Abstract

Background: This study aimed to explore relationship among RANTES -28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism, level of self-expression, and type 2 diabetes mellitus (T2DM).

Materials and methods: Clinical data were collected from 92 subjects with normal blood glucose (NC) and 97 patients with T2DM (DM). CCR5 levels on the surface of monocyte/lymphocyte and plasma RANTES levels were detected by flow cytometry. TaqMan real-time fluorescent quantitative PCR was used to detect genetic polymorphisms of RANTES rs2280788 and CCR5 rs1799987.

Results: There were no significant differences in frequencies of CCR5 rs1799987 genotype and A/G allele and frequencies of RANTES rs2280788 genotype and C/G allele, between subjects in NC and DM group (P > 0.05). Plasma RANTES level in DM group was significantly lower than NC group (P < 0.05), and difference came from patients with T2DM using insulin and subjects with normal blood glucose. CCR5 levels on the surface of monocytes and lymphocytes of patients in DM group were higher than NC group (P < 0.05). There was no significant difference in CCR5 level on the surface of monocytes and lymphocytes (or plasma RANTES level) among different genotypes of CCR5 rs1799987 (or RANTES rs2280788) (P > 0.05). RANTES level was positively correlated with age and TC and negatively correlated with diabetes course and HbA1c. CCR5 level on the surface of monocytes was positively correlated with drinking years, HbA1c, course of diabetes, and negatively correlated with TC. CCR5 on lymphocyte surface was positively correlated with diabetes course, smoking years, HbA1c, and negatively correlated with LDL, TC, HDL (P < 0.05).

Conclusion: RANTES -28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism may not be associated with T2DM of Han nationality in Kunming and cannot affect RANTES and CCR5 expression. RANTES and CCR5 levels may be related to T2DM but may also be affected by age, blood lipids, HbA1c, diabetes course, drugs, and other factors.

Keywords: CCR5; RANTES; cytokines; gene polymorphism; inflammation; type 2 diabetes.

Grants and funding

This study was granted by the National Natural Science Fund of China (Grant No. 82160165, 81160104, and 30760087), the “famous doctor” special program of Yunnan Xingdian Talent support plan in 2022 (Grant NO. RLMY20220009), the Training plan for medical discipline leaders of Yunnan provincial health and family planning commission (Grant NO. D-2017039), the young and middle-aged academic and technical leaders reserve talented person project in Yunnan province (Grant NO. 202105AC160093), the science and technology innovation team foundation of Kunming Medical University (Grant NO.CXTD202101) and the subproject of clinical medical research center for metabolic diseases of Yunnan province (Grant No.202102AA100056).