Original Article | Published:

A common deletion in the haptoglobin gene associated with blood cholesterol levels among Chinese women

Journal of Human Genetics volume 62, pages 911914 (2017) | Download Citation


Haptoglobin (HP) protein plays a critical role in binding and removing free hemoglobin from blood. A deletion in the HP gene affects the protein structure and function. A recent study developed a novel method to impute this variant and discovered significant association of this variant with low-density lipoprotein (LDL) and total cholesterol levels among European descendants. In the present study, we investigated this variant among 3608 Chinese women. Consistent with findings from Europeans, we found significant associations between the deletion with lower cholesterol levels; women homozygous for the deletion allele (HP1–HP1), had a lower level of total cholesterol (−4.24 mg dl–1, P=0.02) and LDL cholesterol (−3.43 mg dl–1, P=0.03) than those not carrying the deletion allele (HP2HP2). Especially, women carrying the HP1S–HP1S, had an even lower level of total cholesterol (−5.59 mg dl–1, P=7.0 × 10–3) and LDL cholesterol (−4.68 mg dl–1, P=8.0 × 10–3) compared to those carrying HP2HP2. These associations remained significant after an adjustment for an established cholesterol level-related variant, rs2000999. Our study extends the previous findings regarding the association of HP structure variant with blood cholesterol levels to East Asians and affirms the validity of the new methodology for assessing HP structure variation.

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The Shanghai Breast Cancer Study is supported by a grant from the National Institutes of Health, R01CA064277; the Shanghai Women’s Health Study is supported by the National Institutes of Health grants R37CA070867 and UM1CA182910. Additional support includes HL126671 to JAB We would like to thank Dr. Boettger for providing the reference panel for SNP haplotype imputation of HP polymorphisms.

Author information


  1. Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA

    • Neil S Zheng
    • , Lisa A Bastarache
    •  & Joshua C Denny
  2. Yale College, Yale University, New Haven, CT, USA

    • Neil S Zheng
  3. Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    • Julie A Bastarache
    •  & Lorraine B Ware
  4. Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA

    • Yingchang Lu
    • , Xiao-Ou Shu
    •  & Jirong Long
  5. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    • Lorraine B Ware


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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Jirong Long.

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Supplementary Information accompanies the paper on Journal of Human Genetics website (http://www.nature.com/jhg)

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