Association between rs1761667 CD36 Polymorphism and Stroke Risk in Korean Type 2 Diabetes Patients

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Association between rs1761667 CD36 Polymorphism and Stroke Risk in Korean Type 2 Diabetes Patients

Introduction

Stroke is a major concern, especially for those with type 2 diabetes mellitus (T2DM). Did you know that the prevalence of stroke in the general population is two to three times less than among T2DM patients? And in T2DM patients, stroke accounts for 11.0% of all deaths. CD36, a scavenger receptor involved in inflammation, innate immunity, and lipid metabolism, has been linked to atherosclerosis pathophysiology. But until now, there was no study on how CD36 polymorphism affects T2DM patients based on disease duration. This study from Chungbuk National University aims to fill that gap.

Study Design and Methods

Participants

A total of 759 T2DM patients who visited Chungbuk National University Hospital from January 2015 to December 2018 were included. Diabetes mellitus (DM) diagnoses followed American Diabetes Association guidelines. Both microvascular (like retinopathy, nephropathy, peripheral neuropathy) and macrovascular (cardiovascular disease, stroke, peripheral artery disease) complications were evaluated.

CD36 Polymorphism Detection

CD36 (rs1761667) polymorphisms were detected using TaqMan probe – based real – time polymerase chain reaction (PCR). The genotyping master mix (ThermoFisher, Cat# 4371353) was used in a 25 mL reaction. Reactions were cycled with preheating at 95°C for 10 min, followed by 40 cycles at 95°C for 15 s and 60°C for 60 s. Fluorescence was detected at each cycle end, and genotype data (GG, AG, or AA) were generated with a BioRad CFX96 Real – Time PCR system.

Statistical Analyses

The Hardy – Weinberg equilibrium probability was tested with the Chi – squared test. Data were expressed as mean ± standard deviation (continuous variables) or percentages (categorical variables). Baseline characteristics were compared with Student’s t – test (continuous variables) and Chi – squared test (categorical parameters). The Chi – squared test evaluated prevalence differences by genotype. Multiple logistic regression analyzed stroke risk factors (age, body mass index (BMI), hypertension, hemoglobin A1c (HbA1c), low – density lipoprotein (LDL) – cholesterol). SPSS for Windows (22.0) was used, with P < 0.05 as significant.

Results

Genotype Distribution

The genotypic distribution of CD36 met Hardy – Weinberg equilibrium (P = 0.946). The frequencies were: GG (51.5%, n = 391), AG (40.4%, n = 307), and AA (8.0%, n = 61). Baseline characteristics showed no significant differences between GG and AG + AA genotypes. The mean age was 61.4 ± 12.4 years (range 19.0 – 91.0), BMI 25.8 ± 3.8 kg/m² (range 15.8 – 41.1), mean T2DM duration 10.5 ± 7.9 years, and 55.2% were men.

Stroke Prevalence by Genotype and Subgroups

  • By Sex: There was a higher stroke prevalence among men with AG + AA genotypes (16.3%) than GG (10.2%, P = 0.049).
  • By Disease Duration: In men with T2DM duration 10 years (15.7% vs. 16.0%, P = 0.946) and women (AG + AA vs. GG: 8.1% vs. 5.9%, P = 0.435), there were no significant differences. No associations were found for cardiovascular disease, peripheral artery disease, or microvascular complications with rs1761667 CD36 SNP in either sex.

Discussion

Association with Stroke

This study found an association between CD36 rs1761667 SNP and stroke in Korean men with T2DM, especially those with shorter disease duration. Previous studies, like Ikram et al [3] (CD36 (rs3211928) polymorphism in Caucasians) and Zhang et al [4] (CD36 (rs1761667 and rs3211928) polymorphisms in Chinese Han for ischemic stroke), have shown related associations. This study is the first in an Asian T2DM population. CD36 expression is up – regulated in hyperglycemia, and polymorphisms may affect lipid metabolism (e.g., decreased oxidized LDL uptake, reduced lipid clearance, increased atherosclerosis and stroke risk [5]).

Limitations and Strengths

  • Limitations: No direct evaluation of CD36 expression by genotype (due to retrospective design, possible recall bias or missing data, lower stroke prevalence). Also, unable to show the influence on stroke clinical course.
  • Strengths: Relatively large sample size compared to previous studies. Comprehensive evaluation of diabetic complications (micro and macrovascular) by disease duration.

Conclusion

The rs1761667 CD36 SNP is associated with stroke in Korean T2DM patients, particularly in male patients with relatively short DM duration. Larger population studies considering various cerebrovascular disease parameters are needed to validate these findings.

References:

  1. Tun NN, Arunagirinathan G, Munshi SK, Pappachan JM. Diabetes mellitus and stroke: a clinical update. World J Diabetes 2017;8:235–248. doi: 10.4239/wjd.v8.i6.235.
  2. Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis – dependent inhibition of neovascularization by thrombospondin – 1. Nat Med 2000;6:41–48. doi: 10.1038/71517.
  3. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med 2009;360:1718–1728. doi: 10.1056/NEJMoa0900094.
  4. Zhang Y, Zang J, Wang B, Li B, Yao X, Zhao H, et al. CD36 genotype associated with ischemic stroke in Chinese Han. Int J Clin Exp Med 2015;8:16149–16157.
  5. Kanoke A, Nishijima Y, Ljungberg M, Omodaka S, Yang SY, Wong S, et al. The effect of type 2 diabetes on CD36 expression and the uptake of oxLDL: diabetes affects CD36 and oxLDL uptake. Exp Neurol 2020;334:113461. doi: 10.1016/j.expneurol.2020.113461.

DOI: 10.1097/CM9.0000000000001501

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