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Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han population

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Abstract

Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case–control study and in a family-based association study. Case–control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the ‘G’ allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the ‘A’ allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z =−1.882, P = 0.049; Z =−2.000, P = 0.045; Z =−2.319, P = 0.020; Z =−2.002, P = 0.045; Z =−2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30600199 and 81200838), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ([2013]1972) and the Foundation of Hunan Science and Technology Committee (2014FJ3138). We acknowledge Joseph C. LaManna, Kui Xu, Girriso Benderro and Suzanne Foss of Case Western Reserve University, Cleveland, USA, for their help in editing this manuscript.

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Authors and Affiliations

  1. Department of Geriatrics, Central South University, Changsha, Hunan, 410011, People’s Republic of China

    YI ZENG

  2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    LE ZHANG, QIDONG YANG, MINGMING MA, BAOQIONG LIU, JIAN XIA, HONGWEI XU, YUNHAI LIU & XIAOPING DU

  3. Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China

    ZHIPING HU

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  1. YI ZENG
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[Zeng Y., Zhang L., Hu Z., Yang Q., Ma M., Liu B., Xia J., Xu H., Liu Y. and Du X. 2016 Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han population. J. Genet. 95, xx–xx]

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ZENG, Y., ZHANG, L., HU, Z. et al. Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han population. J Genet 95, 383–388 (2016). https://doi.org/10.1007/s12041-016-0651-0

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  • DOI: https://doi.org/10.1007/s12041-016-0651-0

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