Abstract 3459: Human Atrial Natriuretic Peptide (ANP) Gene Is Associated With Metabolic Syndrome In The French Population
Background: ANP is important in hemodynamics, but also in lipolysis, particularly in overweight. Its plasmatic concentration is related to number of metabolic syndrome components. Its gene, NPPA, was considered as a candidate for susceptibility to metabolic disorders.
Aims-Methods: We assessed the effect of 3 Hapmap-tagged haplotypes-defining NPPA SNPs, G664A (rs5063), 708C>T (rs5064) and 2238T>C (rs5065) on metabolic parameters levels and metabolic syndrome and their interaction with overweight in a cohort study included 2,576 men and 2,636 women from the general population, followed for 9 years.
Results: In the whole population, there was a significant effect of the 708C>T SNP on waist girth (CC: 83.5 ± 0.1cm, CT: 83.1 ± 0.2 and TT: 81.2 ± 0.9, p=0.04) and HDL-C (CC: 1.63 ± 0.01 mM CT: 1.63 ± 0.01 and TT: 1.77 ± 0.03, p=0.04). The 708C>T SNP interacted with overweight on triglycerides (TG) and waist girth (p=0.002 and p=0.03 respectively for interaction) and in overweight subjects, was associated with TG (CC: 1.51 ± 0.03mM, CT: 1.37 ± 0.07 and TT: 1.13 ± 0.31, p=0.009) and waist girth (CC: 93.1 ± 0.2cm, CT: 92.1 ± 0.4 and TT: 89.1 ± 1.8, p=0.009). The 2238T>C SNP interacted with overweight on waist girth (p=0.08 for interaction) and in overweight subjects, was associated with waist girth (TT: 93.1 ± 0.2cm, TC: 92.4 ± 0.3 and CC: 91.1 ± 0.9, p=0.03). The overweight 708TT carriers and 2238CC carriers had a lower risk of metabolic syndrome (MS) during the 9-year follow-up (rare allele OR=0.74, p=0.043 and 0.75, p=0.017 respectively). No association was found with 664G>A. Haplotype GTC (carrying the minor allele of 708C>T) was significantly associated with lower waist girth level (p=0.007) and TG (p=0.02) in overweight subjects, and with a lower risk of developing MS during follow-up (p=0.02) in overweight subjects.
Conclusion: NPPA tagged SNPs and haplotypes are associated with cardiovascular risk in the general French population through association with lipids, waist girth levels and with incidence of MS in particular in overweight subjects.