Sex-Specific Variations in the mRNA Levels of Candidate Genes in Peripheral Blood Mononuclear Cells from Patients with Diabetes: A Multistep Study

ABSTRACT

Background

Type 2 diabetes (T2D) is one of the most prevalent diseases that also show sexual dimorphism in many different aspects.

Objectives

This study aimed to distinguish the mRNA expression of genes in peripheral blood mononuclear cells (PBMCs) in men or women with T2D using a multistep analysis.

Methods

A total of 95 patients with T2D were compared based on their sex in terms of clinical variables and mRNA expression in their PBMCs.

Results

Men with T2D had lower LDLC, HDLC, and HbA1c values in their blood, but greater creatinine levels. In men with T2D, TLR4, CCR2, NOX2, and p67phox mRNA expression was greater, but IL6 and NF-κB mRNA expression was lesser in PBMCs. There was a link between fasting plasma glucose (FPG), triglycerides, and hs-CRP, as well as COX1 mRNA in men with T2D. In women with T2D, FPG was associated with the mRNA expression of THBS1 and p67phox, as well as triglycerides and HDLC levels. We found the exclusive effect of FPG on HDLC, HbA1c, as well as p67phox mRNA in PBMCs of women with T2D. Analysis revealed the exclusive effect of FPG on hs-CRP and PAFR mRNA in PBMCs of men with T2D. FPG was shown to be associated with body mass index, hs-CRP, triglycerides, and COX1 mRNA in men with T2D, and with serum triglycerides, THSB1, and p67phox mRNA in women with T2D, according to network analysis. HbA1c was linked with NF-κB mRNA in women with T2D.

Conclusions

Using a multistep analysis, it was shown that network analysis outperformed traditional analytic techniques in identifying sex-specific alterations in mRNA gene expression in PBMCs of T2D patients. The development of sex-specific therapeutic approaches may result from an understanding of these disparities.

KEYWORDS:

• Diabetes
• mRNA gene expression
• multistep analysis
• PBMCs
• sex-specific differences

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Author Contributions

YC and DF wrote the original draft; ZC, YL, and QX provided conceptualization, formal analysis, investigation, and methodology; YC and DF involved in data collection; RK performed data analysis, data visualization, and manuscript revision. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

Data Availability Statement

The raw data can be obtained on request from the corresponding author.

Ethical Approval

The study was approved by the University Ethics Committee, and all subjects provided signed informed permission before participation.

Informed Consent

All patients gave informed consent.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/07435800.2023.2280571

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.