Key result
In diabetic patients with CVD, homozygotes for the APOA4 S347 allele had significantly lower total antioxidant status compared with TT and TS subjects (31.2% vs 42.5%; P=0.0024).
Why the study?
Is the APOA4 T347S variant associated with reduced total antioxidant status in diabetic patients with or without cardiovascular disease?
Observational (n=705)
Is the APOA4 T347S variant associated with reduced total antioxidant status in diabetic patients with or without cardiovascular disease?
Absolute Event Rate: 31.2% vs 42.5%
p-value: p=0.0024
The APOA4 S347 rare allele is associated with reduced total antioxidant status in diabetic patients with cardiovascular disease, suggesting a mechanism for its link to increased CHD risk.
Supports mechanistic hypothesis for APOA4 S347 in diabetic CVD; hypothesis-generating and should not change practice.
Apolipoprotein A-IV (apoA-IV) has been postulated to be antiatherogenic. Transgenic APOA4/Apoe-/- mice are protected against atherosclerosis, with plasma apoA-IV displaying antioxidant activity in vitro. In humans, there is an inverse relationship between apoA-IV levels and risk of coronary heart disease (CHD). Furthermore, the APOA4 T347S rare allele has been associated with increased risk of CHD and reduced apoA-IV levels. Reduced total antioxidant status (TAOS) due to increased oxidative stress is implicated in the process of atherogenesis. Thus, this study aimed to examine the association between the APOA4 T347S variant and TAOS in diabetic patients with (n = 196) or without (n = 509) cardiovascular disease (CVD). A higher percentage of CVD patients were present in the lowest quartile of TAOS, compared with the rest (P = 0.04). Overall, there was no association between genotype and TAOS. However, in patients with CVD, homozygotes for the S347 allele had significantly lower TAOS compared with TT and TS subjects (31.2 +/- 9.89% and 42.5 +/- 13.04% TAOS, respectively; P = 0.0024), an effect that was not seen in the patients without CVD. This study offers direct support for an antioxidant capacity of apoA-IV, thus providing some explanation for the antiatherogenic role of apoA-IV and the higher CVD risk in S347 homozygotes.
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Wong et al. (2004) conducted an observational in Diabetes mellitus with or without cardiovascular disease (n=705). APOA4 T347S variant (S347 homozygotes) vs. TT and TS genotypes was evaluated on Total antioxidant status (TAOS) (p=0.0024). In diabetic patients with CVD, homozygotes for the APOA4 S347 allele had significantly lower total antioxidant status compared with TT and TS subjects (31.2% vs 42.5%; P=0.0024).
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