TY - JOUR
T1 - Complement C3 and Risk of Diabetic Microvascular Disease
T2 - A Cohort Study of 95202 Individuals from the General Population
AU - Rasmussen, Katrine Laura
AU - Nordestgaard, Børge Grønne
AU - Nielsen, Sune Fallgaard
N1 - © 2018 American Association for Clinical Chemistry.
PY - 2018/7
Y1 - 2018/7
N2 - BACKGROUND: Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population.METHODS: We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013. Rs1065489, rs429608, and rs448260 were identified with genome-wide association scans in 3752 individuals from the Copenhagen City Heart Study.RESULTS: The cumulative incidence was increased from the lowest tertile to the highest tertile of complement C3 for diabetic retinopathy (log-rank trend, P = 1 × 10-20), nephropathy (P = 7 × 10-15), and neuropathy (P = 5 × 10-10). Multifactorially adjusted hazard ratios for a 1 SD higher concentration of complement C3 were 1.87 (95% CI, 1.61-2.18) for diabetic retinopathy, 1.90 (1.62-2.23) for diabetic nephropathy, and 1.56 (1.29-1.89) for diabetic neuropathy. The multifactorially adjusted hazard ratio for individuals with the highest vs lowest tertile of complement C3 was 3.29 (1.78-6.07) for retinopathy, 2.71 (1.42-5.16) for nephropathy, and 2.40 (1.26-4.54) for neuropathy.CONCLUSIONS: High baseline concentrations of complement C3 were associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. These epidemiological findings were substantiated by a Mendelian randomization approach, potentially indicating causality.
AB - BACKGROUND: Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population.METHODS: We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013. Rs1065489, rs429608, and rs448260 were identified with genome-wide association scans in 3752 individuals from the Copenhagen City Heart Study.RESULTS: The cumulative incidence was increased from the lowest tertile to the highest tertile of complement C3 for diabetic retinopathy (log-rank trend, P = 1 × 10-20), nephropathy (P = 7 × 10-15), and neuropathy (P = 5 × 10-10). Multifactorially adjusted hazard ratios for a 1 SD higher concentration of complement C3 were 1.87 (95% CI, 1.61-2.18) for diabetic retinopathy, 1.90 (1.62-2.23) for diabetic nephropathy, and 1.56 (1.29-1.89) for diabetic neuropathy. The multifactorially adjusted hazard ratio for individuals with the highest vs lowest tertile of complement C3 was 3.29 (1.78-6.07) for retinopathy, 2.71 (1.42-5.16) for nephropathy, and 2.40 (1.26-4.54) for neuropathy.CONCLUSIONS: High baseline concentrations of complement C3 were associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. These epidemiological findings were substantiated by a Mendelian randomization approach, potentially indicating causality.
U2 - 10.1373/clinchem.2018.287581
DO - 10.1373/clinchem.2018.287581
M3 - Journal article
C2 - 29523638
SN - 0009-9147
VL - 64
SP - 1113
EP - 1124
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 7
ER -
