Why the study?
It remained to be determined which single nucleotide polymorphisms within transcriptional pathways of glucose and lipid metabolism are related to multiple features of the metabolic syndrome.
Are genetic variants in lipid and glucose metabolism pathways associated with multiple features of the metabolic syndrome in adults?
Cohort (n=3,575)
Are genetic variants in lipid and glucose metabolism pathways associated with multiple features of the metabolic syndrome in adults?
Relative Risk: 0.76 (95% CI 0.69–0.86)
p-value: p=<0.0001
Genetic variants in CETP and APOE are independently associated with both low HDL-cholesterol and abdominal obesity, helping explain the frequent co-occurrence of these metabolic syndrome features.
May clarify shared pathways in metabolic syndrome; hypothesis-generating and should not yet alter risk assessment or practice.
BACKGROUND: Our objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS). METHODS: 373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence of MetS features, i.e. hyperglycemia, abdominal obesity, decreased HDL-cholesterol levels and hypertension, were measured twice in 6 years. Associations between the SNPs and the individual MetS features were analyzed by log-linear models. For SNPs related to multiple MetS features (P < 0.01), we investigated whether these associations were independent of each other. RESULTS: Two SNPs, CETP Ile405Val and APOE Cys112Arg, were associated with both the prevalence of low HDL-cholesterol level (Ile405Val P = < .0001; Cys112Arg P = 0.001) and with the prevalence of abdominal obesity (Ile405Val P = 0.007; Cys112Arg P = 0.007). For both SNPs, the association with HDL-cholesterol was partly independent of the association with abdominal obesity and vice versa. CONCLUSION: Two SNPs, mainly known for their role in lipid metabolism, were associated with two MetS features i.e., low HDL-cholesterol concentration, as well as, independent of this association, abdominal obesity. These SNPs may help to explain why low HDL-cholesterol levels and abdominal obesity frequently co-occur.
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Povel et al. (2011) conducted a cohort in Metabolic Syndrome (n=3,575). CETP Ile405Val and APOE Cys112Arg SNPs vs. Major allele carriers was evaluated on Prevalence of low HDL-cholesterol (CETP Ile405Val minor allele) (PR 0.76, 95% CI 0.69-0.86, p=<0.0001).
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