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

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 relationships between fasting complement markers and cardiometabolic risk in BA and White European (WE) men, and whether postprandial complement response differs by ethnicity. Eighty-eight BA and 97 WE men [age = 44.4 (42.0-47.6) yr, body mass index (BMI) = 29.2 ± 4.5 kg·m^-2] were assessed for fasting plasma complement markers and cardiometabolic risk factors. A second cohort (<i>n</i> = 20 men, 10 BA) [age = 31.0 ± 1.1 yr, BMI = 27.1 (26.0-28.6) kg·m^-2] men underwent a moderate-to-high-fat feeding protocol to measure postprandial plasma complement, serum insulin, plasma glucose, triacylglycerol (TAG), and nonesterified 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 terminal complement complex and (both total and LDL)-cholesterol were only observed in the WE cohort. There was a trend toward ethnic differences in postprandial Factor D (<i>P</i> = 0.097) and iC3b (<i>P</i> = 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.<b>NEW & NOTEWORTHY</b> The present study found that markers of the complement system were less strongly associated with adiposity and lipid profiles in Black African men compared with White European men, suggesting ethnic differences in the determinants of complement production and activation. In Black African men, adipose tissue may play a less important role in complement production and activation and also in the link with traditional cardiometabolic risk factors.