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

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

^*Corresponding author for this work

Nutrition, Metabolism and Genomics

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	dgac598
Pages (from-to)	931-940
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	108
Issue number	4
Early online date	20 Oct 2022
DOIs	https://doi.org/10.1210/clinem/dgac598
Publication status	Published - 10 Mar 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1210/clinem/dgac598Licence: CC BY

https://edepot.wur.nl/584435Licence: CC BY

Cite this

Straat, M. E., Martinez-Tellez, B., van Eyk, H. J., Bizino, M. B., van Veen, S., Vianello, E., Stienstra, R., Ottenhoff, T. H. M., Lamb, H. J., Smit, J. W. A., Jazet, I. M., Rensen, P. C. N., & Boon, M. R. (2023). Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes. Journal of Clinical Endocrinology and Metabolism, 108(4), 931-940. Article dgac598. https://doi.org/10.1210/clinem/dgac598

@article{69ce7199440949428e01bab4cbb70ecd,

title = "Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes",

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.",

author = "Straat, {Maaike E.} and Borja Martinez-Tellez and {van Eyk}, {Huub J.} and Bizino, {Maurice B.} and {van Veen}, Suzanne and Eleonora Vianello and Rinke Stienstra and Ottenhoff, {Tom H.M.} and Lamb, {Hildo J.} and Smit, {Johannes W.A.} and Jazet, {Ingrid M.} and Rensen, {Patrick C.N.} and Boon, {Mari{\"e}tte R.}",

year = "2023",

month = mar,

day = "10",

doi = "10.1210/clinem/dgac598",

language = "English",

volume = "108",

pages = "931--940",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "4",

}

Straat, ME, Martinez-Tellez, B, van Eyk, HJ, Bizino, MB, van Veen, S, Vianello, E, Stienstra, R, Ottenhoff, THM, Lamb, HJ, Smit, JWA, Jazet, IM, Rensen, PCN & Boon, MR 2023, 'Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 108, no. 4, dgac598, pp. 931-940. https://doi.org/10.1210/clinem/dgac598

TY - JOUR

T1 - Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

AU - Straat, Maaike E.

AU - Martinez-Tellez, Borja

AU - van Eyk, Huub J.

AU - Bizino, Maurice B.

AU - van Veen, Suzanne

AU - Vianello, Eleonora

AU - Stienstra, Rinke

AU - Ottenhoff, Tom H.M.

AU - Lamb, Hildo J.

AU - Smit, Johannes W.A.

AU - Jazet, Ingrid M.

AU - Rensen, Patrick C.N.

AU - Boon, Mariëtte R.

PY - 2023/3/10

Y1 - 2023/3/10

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgac598

DO - 10.1210/clinem/dgac598

M3 - Article

SN - 0021-972X

VL - 108

SP - 931

EP - 940

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 4

M1 - dgac598

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this