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The calcium-sensing receptor R990G polymorphism is associated with increased risk of hypertriglyceridemia in obese Chinese
Authors:Yong-han He  Wei-lan Kong  Guan Wang  Yue Zhao  Ming-xin Bi  Li-xin Na  Mao-qing Wang  Ben Perry  Ying Li
Affiliation:1. National Key Discipline of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, China;2. The First Affiliated Hospital, Harbin Medical University, China;3. Institute for Nutrisciences and Health, National Research Council Canada, Charlottetown, PE, Canada;4. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
Abstract:

Background

We have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese.

Methods

A total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3 years later.

Results

There were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (p < 0.001). After stratification, in obese subjects, the homozygous (G/G) distribution of the CaSR R990G polymorphism in the HTG group was significantly higher than in the NTG group (p = 0.001), and showed an increased risk of HTG at baseline [OR = 2.55, 95% CI = 1.65–3.92, p < 0.006]. Interaction of the CaSR R990G polymorphism with BMI was associated with increased risk of HTG (β = 0.927, p < 0.001). Re-evaluation of the NTG subjects revealed significantly increased serum triglyceride levels in obese homozygous versus wildtype carriers (p < 0.05).

Conclusions

These results suggest that the CaSR R990G polymorphism is associated with increased risk of HTG, especially in obese Chinese, and may be a potential genetic predictor of diseases related to HTG.
Keywords:BMI, Body mass index   CAD, Coronary artery disease   cAMP, Adenosine 3&prime  , 5&prime  -cyclic monophosphate   CaSR, Calcium-sensing receptor   HTG, Hypertriglyceridemia   MI, Myocardial infarction   MTP, Microsomal triglyceride transfer protein   NTG, Normal triglyceride   OR, Odds ratio   PCR, Polymerase chain reaction   PTH, Parathyroid hormone   SD, Standard deviation   TC, Total cholesterol   TG, Triglyceride   VLDL, Very-low-density lipoprotein   WHR, Waist&ndash  hip ratio
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