Influence of multiple apolipoprotein A-I and B genetic variations on insulin resistance and metabolic syndrome in obstructive sleep apnea

Abstract Background: The relationships between apolipoprotein A-I (APOA-I), apolipoprotein B (APOB) with insulin resistance, metabolic syndrome (MetS) are unclear in OSA. We aimed to evaluate whether the multiple single nucleotide polymorphism (SNP) variants of APOA-I and APOB exert a collaborative effect on insulin resistance and MetS in OSA. Methods: Initially, 12 APOA-I SNPs and 30 APOB SNPs in 5,259 subjects were examined. After strict screening, four APOA-I SNPs and five APOB SNPs in 4,007 participants were included. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of APOA-I and APOB. Logistic regression analyses were used to evaluate the relationships between APOA-I/APOB genetic polymorphisms, insulin resistance, and MetS in OSA. Results: Serum APOB levels increased the risk of insulin resistance and MetS adjusting for age, gender and BMI [odds ratio (OR=3.168, P < 0.001; OR=6.098, P < 0.001, respectively]. APOA-I GRS decreased the risk of insulin resistance and MetS after adjustments (OR = 0.917, P = 0.001; OR = 0.870, P < 0.001, respectively). APOB GRS had no association with insulin resistance (OR = 1.364, P =0.610), and had weak association with MetS after adjustments (OR =1.072, P = 0.042). In addition, individuals in the top quintile of the APOA-I genetic score distribution had a lower risk of insulin resistance and MetS after adjustments (OR = 0.761, P = 0.007; OR = 0.637, P < 0.001, respectively). Conclusions: In patients with OSA, cumulative effects of APOA-I genetic variations decreased the risk of insulin resistance and MetS, whereas multiple APOB genetic variations had no associations with insulin resistance and weak association with MetS.