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Association of type 2 diabetes mellitus with the interaction between low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults.
J Diabetes 2017; 9(11):994-1002JD

Abstract

BACKGROUND

Low-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.

METHODS

In all, 7751 subjects aged ≥18 years 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.

RESULTS

Cox 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 β-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).

CONCLUSIONS

The risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to β-cell function and lipid metabolism.

Authors+Show Affiliations

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Discipline of Public Health and Preventive Medicine, Center of Preventive Medicine Research and Assessment, Henan University of Traditional Chinese Medicine, Zhengzhou, China.Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China. Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, China.Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China. Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28067456

Citation

Zhang, Lu, et al. "Association of Type 2 Diabetes Mellitus With the Interaction Between Low-density Lipoprotein Receptor-related Protein 5 (LRP5) Polymorphisms and Overweight and Obesity in Rural Chinese Adults." Journal of Diabetes, vol. 9, no. 11, 2017, pp. 994-1002.
Zhang L, Wang J, Zhang M, et al. Association of type 2 diabetes mellitus with the interaction between low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults. J Diabetes. 2017;9(11):994-1002.
Zhang, L., Wang, J., Zhang, M., Wang, G., Shen, Y., Wu, D., ... Hu, D. (2017). Association of type 2 diabetes mellitus with the interaction between low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults. Journal of Diabetes, 9(11), pp. 994-1002. doi:10.1111/1753-0407.12522.
Zhang L, et al. Association of Type 2 Diabetes Mellitus With the Interaction Between Low-density Lipoprotein Receptor-related Protein 5 (LRP5) Polymorphisms and Overweight and Obesity in Rural Chinese Adults. J Diabetes. 2017;9(11):994-1002. PubMed PMID: 28067456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of type 2 diabetes mellitus with the interaction between low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults. AU - Zhang,Lu, AU - Wang,Jinjin, AU - Zhang,Ming, AU - Wang,Guo'an, AU - Shen,Yanxia, AU - Wu,Dongting, AU - Wang,Chongjian, AU - Li,Linlin, AU - Ren,Yongcheng, AU - Wang,Bingyuan, AU - Zhang,Hongyan, AU - Yang,Xiangyu, AU - Zhao,Yang, AU - Han,Chengyi, AU - Zhou,Junmei, AU - Pang,Chao, AU - Yin,Lei, AU - Zhao,Jingzhi, AU - Luo,Xinping, AU - Hu,Dongsheng, Y1 - 2017/03/02/ PY - 2016/09/05/received PY - 2016/11/28/revised PY - 2017/01/03/accepted PY - 2017/1/10/pubmed PY - 2018/6/13/medline PY - 2017/1/10/entrez KW - Chinese KW - 2型糖尿病 KW - cohort study KW - interaction KW - low-density lipoprotein receptor-related protein 5 (LRP5) KW - type 2 diabetes mellitus KW - 中国人 KW - 交互作用 KW - 低密度脂蛋白受体相关蛋白5 KW - 队列研究 SP - 994 EP - 1002 JF - Journal of diabetes JO - J Diabetes VL - 9 IS - 11 N2 - BACKGROUND: Low-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. METHODS: In all, 7751 subjects aged ≥18 years 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. RESULTS: Cox 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 β-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). CONCLUSIONS: The risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to β-cell function and lipid metabolism. SN - 1753-0407 UR - https://www.unboundmedicine.com/medline/citation/28067456/Association_of_type_2_diabetes_mellitus_with_the_interaction_between_low_density_lipoprotein_receptor_related_protein_5__LRP5__polymorphisms_and_overweight_and_obesity_in_rural_Chinese_adults_ L2 - https://doi.org/10.1111/1753-0407.12522 DB - PRIME DP - Unbound Medicine ER -