基于基因网络和遗传风险评分分析下的钙补充和糖尿病风险因素关系的影响

Although evidence from observational studies have been suggested that calcium deficiency was significantly associated with increased risk of obesity, metabolic syndrome, dyslipidemia and type 2 diabetes, results of clinical intervention studies were inconsistent or contradictory. The variability caused by genetic differences may be the primary reason that leads to the above inconsistent results. Therefore, examining the impact of genetic factors on the association between calcium supplement and health effects may yield important knowledge about how to develop different calcium intervention plans for different individuals and take targeted interventions to prevent diseases effectively. Based on clinical calcium supplement intervention research, this research plan to screen and identify common gene polymorphisms that can simultaneously influence calcium metabolism and diabetes development. On the basis of these genes, the gene regulation network is constructed by using biological information technology to analyze the effect of complex interaction among genes on the association between calcium supplement and diabetes-related risk factors. In addition, based on the gene network of our country residents, a calcium and diabetes genetic risk score could be developed , which can clearly assess calcium demand for individuals, and establish individual different calcium supplementation scheme, providing a theoretical basis and practical evidence for our individual nutrition intervention on chronic diseases in China.

虽然观察性研究证据表明钙缺乏与慢性病，例如，肥胖、代谢综合征、高脂血症和糖尿病的患病风险增高显著相关，但是临床干预研究却出现不一致，甚至相互矛盾的情况。临床研究结论的不一致，推测其原因，很可能是由于遗传因素影响的个体差异的存在导致研究结果的不一致。因此，阐明遗传因素与钙补充之间的关系如何影响人群健康，从而针对不同个体制定不同的钙干预方案，采取有针对性的干预措施，有效预防疾病至关重要。本次研究以临床钙补充干预研究为切入点，筛选和鉴别出可以同时影响钙吸收代谢和糖尿病发生发展的共同的基因多态性，并以这些基因为基础，利用生物信息技术构建基因调控网络，基于基因网络分析补钙和糖尿病危险因素的关系，并在此基础上建立基于我国居民遗传背景下的钙和糖尿病遗传风险评分，从而根据遗传风险评分明确我国居民不同个体钙需求量，制定居民个体化钙补充干预方案，并为我国慢性病营养个体化干预研究提供理论依据和可行证据。

我国数次营养调查的结果均表明，我国居民钙摄入量和膳食推荐摄入量的800mg/d仍然有很大的差距，因此“补钙热”一直在我国没有降温。钙片一直是我国居民、特别是老年人常见的膳食补充剂。虽然之前的一些研究结果发现钙缺乏会导致肥胖、胰岛素抵抗、高血糖以及2型糖尿病风险增加，甚至一些临床随机对照实验结果还证明补钙可能会在预防2型糖尿病方面发挥积极的作用。本项目研究发现，在超重/肥胖高风险居民中，并不是所有人补钙都会有预防2型糖尿病的作用。只有糖尿病遗传易感性高风险的个体才需要在预防2型糖尿病过程中，进行补钙干预，从而发挥如前期文献报道的降低血糖、胰岛素抵抗、提高胰岛素分泌的作用；同时本身钙需求遗传风险较低个体或糖尿病遗传易感性较低个体补钙需要慎重，因为这部分个体长期补钙不仅不会发挥上述研究中钙预防2型糖尿病的有益作用，甚至还可能会增加颈动脉内膜厚度，引起心血管疾病以及中风的发病风险增加。本次项目为以后我国居民补钙干预提供了临床随机对照实验证据以及个体化干预依据。