Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

Maaike E Straat; Borja Martinez-Tellez; Huub J van Eyk; Maurice B Bizino; Suzanne van Veen; Eleonora Vianello; Rinke Stienstra; Tom H M Ottenhoff; Hildo J Lamb; Johannes W A Smit; Ingrid M Jazet; Patrick C N Rensen; Mariëtte R Boon

doi:10.1210/clinem/dgac598

Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

J Clin Endocrinol Metab. 2023 Mar 10;108(4):931-940. doi: 10.1210/clinem/dgac598.

Authors

Maaike E Straat^{1

2}, Borja Martinez-Tellez^{1

2}, Huub J van Eyk^{1

2}, Maurice B Bizino^{1

3}, Suzanne van Veen⁴, Eleonora Vianello⁴, Rinke Stienstra^{5

6}, Tom H M Ottenhoff⁴, Hildo J Lamb³, Johannes W A Smit⁶, Ingrid M Jazet^{1

2}, Patrick C N Rensen^{1

2}, Mariëtte R Boon^{1

2}

Affiliations

¹ Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
² Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
³ Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
⁴ Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
⁵ Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708 PB Wageningen, the Netherlands.
⁶ Department of Medicine, Radboud University Medical Center, 6525 XZ Nijmegen, the Netherlands.

Abstract

Context: South Asian individuals are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and progression of T2D, this factor is still underexplored in South Asians.

Objective: This work aimed to study whether circulating messenger RNA (mRNA) transcripts of immune genes are different between South Asian compared with Europid patients with T2D.

Methods: A secondary analysis was conducted of 2 randomized controlled trials of Dutch South Asian (n = 45; age: 55 ± 10 years, body mass index [BMI]: 29 ± 4 kg/m2) and Dutch Europid (n = 44; age: 60 ± 7 years, BMI: 32 ± 4 kg/m2) patients with T2D. Main outcome measures included mRNA transcripts of 182 immune genes (microfluidic quantitative polymerase chain reaction; Fluidigm Inc) in fasted whole-blood, ingenuity pathway analyses (Qiagen).

Results: South Asians, compared to Europids, had higher mRNA levels of B-cell markers (CD19, CD79A, CD79B, CR2, CXCR5, IGHD, MS4A1, PAX5; all fold change > 1.3, false discovery rate [FDR] < 0.008) and interferon (IFN)-signaling genes (CD274, GBP1, GBP2, GBP5, FCGR1A/B/CP, IFI16, IFIT3, IFITM1, IFITM3, TAP1; all FC > 1.2, FDR < 0.05). In South Asians, the IFN signaling pathway was the top canonical pathway (z score 2.6; P < .001) and this was accompanied by higher plasma IFN-γ levels (FC = 1.5, FDR = 0.01). Notably, the ethnic difference in gene expression was larger for women (20/182 [11%]) than men (2/182 [1%]).

Conclusion: South Asian patients with T2D show a more activated IFN-signaling pathway compared to Europid patients with T2D, which is more pronounced in women than men. We speculate that a more activated IFN-signaling pathway may contribute to the more rapid progression of T2D in South Asian compared with Europid individuals.

Trial registration: ClinicalTrials.gov NCT01761318 NCT02660047.

Keywords: B lymphocytes; ethnicity; gene expression; interferon gamma; metabolic syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Body Mass Index
Diabetes Mellitus, Type 2* / ethnology
Diabetes Mellitus, Type 2* / genetics
Ethnicity
European People
Female
Humans
Male
Middle Aged
South Asian People

Associated data

ClinicalTrials.gov/NCT01761318
ClinicalTrials.gov/NCT02660047