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The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan

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Abstract

Metabolic syndrome (MetS) is a combination of medical disorders, consisting of multiple, interrelated risk factors of metabolic origin. To investigate the associations of MetS with appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5) polymorphism variants and the joint effect of cigarette smoking and these polymorphism variants on MetS in a community-based case–control study. Metabolic syndrome was defined according to the American Heart Association and National Heart Lung Blood Institute (AHA/NHLBI) criteria. A total of 237 MetS cases and 202 subjects without MetS aged 40 or over in Taiwan were analyzed. The genotypes of LRP5-rs3736228, LEPR-rs1137100, near MC4R-rs17782313 and SH2B1-rs4788102 were analyzed by the PCR–restriction fragment length polymorphism method. A strong association of the SNP rs17782313 near MC4R gene with MetS susceptibility was found. The data indicated that the C allele of near MC4R-rs17782313 is an obvious risk factor for MetS susceptibility. The joint effects of cigarette smoking and susceptible genotypes of LRP5, LEPR, near MC4R or SH2B1 genes led to a relatively higher risk of having MetS. Using subjects with the wild-type of LRP5, LEPR, near MC4R or SH2B1 genes and without a smoking habit as a reference group, those with cigarette smoking (current and former) and more than one variant type had a 4.1-fold (95 % CI = 1.6–10.2) risk of having MetS. The genotypes of the appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5), together with a cigarette smoking habit, are important risk factors for MetS.

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Abbreviations

α-MSH:

α-Melanocyte-stimulating hormone

BMI:

Body mass index

CI:

Confidence intervals

CNS:

Central nervous system

CVD:

Cardiovascular diseases

GLM:

General linear model

HOMA:

Homeostasis model assessment

LDL:

Low density lipoprotein

LEPR:

Leptin receptor

LRP5:

LDL receptor-related protein 5

MC3R:

Melanocortin-3 receptors

MC4R:

Melanocortin-4 receptors

MetS:

Metabolic syndrome

OR:

Odds ratio

POMC:

Pro-opiomelanocortin

SD:

Standard deviation

SH2B1:

Src homology 2 B adaptor protein 1

SNP:

Single nucleotide polymorphisms

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Acknowledgments

This study was supported by grants from China Medical University Hospital (DMR98-088) and the National Science Council of Taiwan (NSC93-2314-B-039-025&NSC94-2314-B-039-024).

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Authors and Affiliations

  1. Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung, Taiwan, ROC

    Chuan-Wei Yang & Cheng-Chieh Lin

  2. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC

    Chuan-Wei Yang, Chia-Ing Li, Chiu-Shong Liu, Da-Tian Bau & Cheng-Chieh Lin

  3. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan, ROC

    Chiu-Shong Liu, Chih-Hsueh Lin, Wen-Yuan Lin & Cheng-Chieh Lin

  4. School of Medicine, College of Medicine, China Medical University, No. 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, ROC

    Chia-Ing Li, Chiu-Shong Liu, Chih-Hsueh Lin, Wen-Yuan Lin & Cheng-Chieh Lin

  5. Terry Fox Cancer Research Laboratory, China Medical University & Hospital, Taichung, Taiwan, ROC

    Da-Tian Bau

  6. Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan, ROC

    Tsai-Chung Li

  7. Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan, ROC

    Tsai-Chung Li

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  1. Chuan-Wei Yang
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  2. Chia-Ing Li
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  7. Tsai-Chung Li
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Correspondence to Tsai-Chung Li or Cheng-Chieh Lin.

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Chia-Ing Li equally contributed as first author.

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Yang, CW., Li, CI., Liu, CS. et al. The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan. Mol Biol Rep 40, 525–533 (2013). https://doi.org/10.1007/s11033-012-2089-7

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  • DOI: https://doi.org/10.1007/s11033-012-2089-7

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