Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uric acid (UA) is the final catabolic product of purine metabolism and elevated levels are associated with diabetes and cardiovascular disease. A recent meta-analysis of genome-wide association studies totalling 28,141 participants identified five novel loci associated with serum UA levels. In our population-based cohort of 7795 subjects, we replicated four of these five loci; PDZK1 (rs12129861, P = 1.07 x 10(-3)), glucokinase regulator protein (GCKR) (rs780094, P = 4.83 x 10(-4)), SLC16A9 (rs742132, P = 0.047) and SLC22A11 (rs17300741, P = 6.13 x 10(-3)), but not LRRC16A (rs742132, P = 0.645). Serum UA concentration is a complex trait, closely associated to renal UA handling (fractional UA excretion, P < 1 x 10(-300)), renal function (serum creatinine, P < 1 x 10(-300)) and the metabolic syndrome (including fasting insulin, P = 2.48 x 10(-232); insulin resistance, P = 2.51 x 10(-258); waist circumference, P < 1 x 10(-300)) and systolic blood pressure (P = 1.93 x 10(-219)). Together these factors explain 67% of the variance in UA levels. Therefore, we sought to determine the potential contribution of these factors to the association of these novel loci with UA levels, by including them as additional explanatory variables in our analyses, and by considering them as alternative response variables. The association with the GCKR locus is attenuated by serum triglycerides and fractional UA excretion. We also observed the GCKR locus to be associated with total cholesterol (P = 7.52 x 10(-6)), triglycerides (P = 2.65 x 10(-9)), fasting glucose (P = 0.011), fractional UA excretion (P = 3.36 x 10(-5)) and high-sensitive CRP (P = 1.18 x 10(-3)) also after adjusting for serum UA levels. We argue that GCKR locus affects serum UA levels through a factor that also affects triglycerides.
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PMID:Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms. 1986 89

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.
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PMID:The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents. 2613 10