Molecular Biology Reports

, Volume 40, Issue 1, pp 525–533 | Cite as

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

  • Chuan-Wei Yang
  • Chia-Ing Li
  • Chiu-Shong Liu
  • Da-Tian Bau
  • Chih-Hsueh Lin
  • Wen-Yuan Lin
  • Tsai-Chung Li
  • Cheng-Chieh Lin


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.


Metabolic syndrome Cigarette smoking MC4R LRP5 SH2B1 Polymorphism 



α-Melanocyte-stimulating hormone


Body mass index


Confidence intervals


Central nervous system


Cardiovascular diseases


General linear model


Homeostasis model assessment


Low density lipoprotein


Leptin receptor


LDL receptor-related protein 5


Melanocortin-3 receptors


Melanocortin-4 receptors


Metabolic syndrome


Odds ratio




Standard deviation


Src homology 2 B adaptor protein 1


Single nucleotide polymorphisms



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).

Supplementary material

11033_2012_2089_MOESM1_ESM.docx (1020 kb)
Supplementary material 1 (DOCX 1,020 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Chuan-Wei Yang
    • 1
    • 2
  • Chia-Ing Li
    • 2
    • 4
  • Chiu-Shong Liu
    • 2
    • 3
    • 4
  • Da-Tian Bau
    • 2
    • 5
  • Chih-Hsueh Lin
    • 3
    • 4
  • Wen-Yuan Lin
    • 3
    • 4
  • Tsai-Chung Li
    • 6
    • 7
  • Cheng-Chieh Lin
    • 1
    • 2
    • 3
    • 4
  1. 1.Ph.D. Program for Aging, College of MedicineChina Medical UniversityTaichungTaiwan, ROC
  2. 2.Department of Medical ResearchChina Medical University HospitalTaichungTaiwan, ROC
  3. 3.Department of Family MedicineChina Medical University HospitalTaichungTaiwan, ROC
  4. 4.School of Medicine, College of MedicineChina Medical UniversityTaichungTaiwan, ROC
  5. 5.Terry Fox Cancer Research LaboratoryChina Medical University & HospitalTaichungTaiwan, ROC
  6. 6.Graduate Institute of Biostatistics, College of Public HealthChina Medical UniversityTaichungTaiwan, ROC
  7. 7.Department of Healthcare Administration, College of Health ScienceAsia UniversityTaichungTaiwan, ROC

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