科研之友
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摘要
BackgroundLow-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism. The present cohort study evaluated associations of LRP5 variants with the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. @@@ MethodsIn all, 7751 subjects aged 18years without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, and 5511 with a clear disease outcome were eligible for analysis. The same questionnaire was administered and the same anthropometric and blood biochemical examinations were performed at baseline and follow-up. Association analysis was performed for five single nucleotide polymorphisms and haplotypes of LRP5. @@@ ResultsCox proportional hazards testing of three different genetic models found no significant association between T2DM and LRP5 after adjusting for potential risk factors (P> 0.05). However, the incidence of T2DM in subjects with LRP5 mutational genotypes was higher in the overweight/obese than normal weight population. Under the dominant model, the risk of T2DM was increased with an interaction between rs11228303 and the waist-to-height ratio adjusted for baseline age, sex, and family history of T2DM (synergy index [SI]=4.172; 95% confidence interval [CI] 1.014-17.166)], and body mass index (SI=3.237; 95% CI 1.102-9.509). Furthermore, the A allele of rs3758644 was related to decreased fasting plasma insulin and homeostatic model assessment of -cell function levels, whereas the T allele of rs12363572 was related to increased high-density lipoprotein cholesterol levels in new-onset diabetes patients (P< 0.05). @@@ ConclusionsThe risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to -cell function and lipid metabolism.
