Plasma complement system markers and their association with cardiometabolic risk factors: an ethnic comparison of White European and Black African men

Reed, Reuben M., Zelek, Wioleta M., Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676, Whelehan, Gráinne, Lockhart, Sam, O'Rahilly, Stephen, Witard, Oliver C., Whyte, Martin B and Goff, Louise M. 2025. Plasma complement system markers and their association with cardiometabolic risk factors: an ethnic comparison of White European and Black African men. Endocrinology and Metabolism 10.1152/ajpendo.00419.2024

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Abstract

Populations of Black African (BA) ancestry are disproportionately affected by cardiometabolic diseases, possibly due to dysregulation of the complement system. This study aimed to determine 1) relationships between fasting complement markers and cardiometabolic risk in BA and White European (WE) men, and 2) whether postprandial complement response differs by ethnicity. Eighty-eight BA and 97 WE men (age=44.4 [42.0-47.6] years, BMI=29.2±4.5 kg/m2) were assessed for fasting plasma complement markers and cardiometabolic risk factors. A second cohort ( n=20 men, 10 BA) (age=31.0±1.1 years, BMI=27.1 [26.0-28.6] kg/m2) men underwent a moderate-to-high-fat feeding protocol to measure postprandial plasma complement, serum insulin, plasma glucose, TAG and non-esterified fatty acids. C4 and Factor D were lower, and iC3b was higher, in BA compared with WE men. C3 and C4 were strongly associated with all adiposity markers in both ethnicities, but the WE cohort showed stronger associations between C3 and subcutaneous adipose tissue, C5 and WC, and iC3b and visceral adipose tissue compared with BA. C3 was associated with all cardiometabolic risk factors in both ethnicities. Associations between C5 and cholesterol, C4 and TAG, and TCC and (both total and LDL)-cholesterol were only observed in the WE cohort. There was a trend towards ethnic differences in postprandial Factor D ( P=0.097) and iC3b ( P=0.085). The weaker associations between the complement system markers with adiposity and lipid profiles in BA compared with WE men suggest ethnic differences in the determinants of complement production and activation, whereby adipose tissue may play a less important role in BA men.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	American Physiological Society
ISSN:	0193-1849
Date of First Compliant Deposit:	18 March 2025
Date of Acceptance:	27 February 2025
Last Modified:	18 Mar 2025 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/176950

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