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Association of single-nucleotide polymorphisms rs2197076 and rs2241883 of FABP1 gene with polycystic ovary syndrome

  • Genetics
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Abstract

Purpose

The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS).

Methods

The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS.

Results

Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883.

Conclusion

In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS.

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References

  1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89:2745–9.

    Article  PubMed  CAS  Google Scholar 

  2. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25.

    Google Scholar 

  3. Traub ML. Assessing and treating insulin resistance in women with polycystic ovarian syndrome. World J Diabetes. 2011;2:33–40.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang ET, Calderon-Margalit R, Cedars MI, Daviglus ML, Merkin SS, Schreiner PJ, et al. Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia. Obstet Gynecol. 2011;117:6–13.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen ZJ, Shi Y. Polycystic ovary syndrome. Front Med China. 2010;4:280–4.

    Article  PubMed  Google Scholar 

  6. Freeman R, Pollack R, Rosenbloom E. Assessing impaired glucose tolerance and insulin resistance in polycystic ovarian syndrome with a muffin test: an alternative to the glucose tolerance test. Endocr Pract. 2010;16:810–7.

    Article  PubMed  Google Scholar 

  7. Kiddy DS, Hamilton-Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 1992;36:105–11.

    Article  CAS  Google Scholar 

  8. Stewart DR, Dombroski BA, Urbanek M, Ankener W, Ewens KG, Wood JR, et al. Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J Clin Endocrinol Metab. 2006;91:4112–7.

    Article  PubMed  CAS  Google Scholar 

  9. Xita N, Georgiou I, Tsatsoulis A. The genetic basis of polycystic ovary syndrome. Eur J Endocrinol. 2002;147:717–25.

    Article  PubMed  CAS  Google Scholar 

  10. Zimmerman AW, Veerkamp JH. New insights into the structure and function of fatty acid-binding proteins. Cell Mol Life Sci. 2002;59:1096–116.

    Article  PubMed  CAS  Google Scholar 

  11. Ordovas JM. Identification of a functional polymorphism at the adipose fatty acid binding protein gene (FABP4) and demonstration of its association with cardiovascular disease: a path to follow. Nutr Rev. 2007;65:130–4.

    Article  PubMed  Google Scholar 

  12. Lara-Castro C, Hunter GR, Lovejoy JC, Gower BA, Fernández JR. Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism and abdominal adipose tissue in African-American and Caucasian women. J Clin Endocrinol Metab. 2005;90:1196–201.

    Article  PubMed  CAS  Google Scholar 

  13. Takakura Y, Yoshioka K, Umekawa T, Kogure A, Toda H, Yoshikawa T, et al. Thr54 allele of the FABP2 gene affects resting metabolic rate and visceral obesity. Diabetes Res Clin Pract. 2005;67:36–42.

    Article  PubMed  CAS  Google Scholar 

  14. Brouillette C, Bossé Y, Pérusse L, Gaudet D, Vohl MC. Effect of liver fatty acid binding protein (FABP) T94A missense mutation on plasma lipoprotein responsiveness to treatment with fenofibrate. J Hum Genet. 2004;49:424–32.

    Article  PubMed  CAS  Google Scholar 

  15. Robitaille J, Brouillette C, Lemieux S, Pérusse L, Gaudet D, Vohl MC. Plasma concentrations of apolipoprotein B are modulated by a gene-diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men. Mol Genet Metab. 2004;82:296–303.

    Article  PubMed  CAS  Google Scholar 

  16. Damcott CM, Moffett SP, Feingold E, Barmada MM, Marshall JA, Hamman RF, et al. Genetic variation in fatty acid-binding protein-4 and peroxisome proliferator-activated receptor gamma interactively influence insulin sensitivity and body composition in males. Metabolism. 2004;53:303–9.

    Article  PubMed  CAS  Google Scholar 

  17. Shin HD, Kim LH, Park BL, Jung HS, Cho YM, Moon MK, et al. Polymorphisms in fatty acid-binding protein-3 (FABP3)—putative association with type 2 diabetes mellitus. Hum Mutat. 2003;22:180.

    Article  PubMed  Google Scholar 

  18. Mansego ML, Martínez F, Martínez-Larrad MT, Zabena C, Rojo G, Morcillo S, et al. Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population. PLoS One. 2012;7:e31853.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Li T, Wu K, You L, Xing X, Wang P, Cui L, et al. Common variant rs9939609 in gene FTO confers risk to polycystic ovary syndrome. PLoS One. 2013;8:e66250.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Housman E, Reynolds RV. Polycystic ovary syndrome: a review for dermatologists: Part I. Diagnosis and manifestations. J Am Acad Dermatol. 2014;71:847. e1-847.e10; quiz 857–8.

    Article  PubMed  Google Scholar 

  21. Glintborg D, Andersen M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol. 2010;26:281–96.

    Article  PubMed  CAS  Google Scholar 

  22. Nam Menke M, Strauss 3rd JF. Genetics of polycystic ovarian syndrome. Clin Obstet Gynecol. 2007;50:188–204.

    Article  PubMed  Google Scholar 

  23. Gilling-Smith C, Willis DS, Beard RW, Franks S. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab. 1994;79:1158–65.

    PubMed  CAS  Google Scholar 

  24. Ha L, Shi Y, Zhao J, Li T, Chen ZJ. Association study between polycystic ovarian syndrome and the susceptibility genes polymorphisms in Hui Chinese women. PLoS One. 2015;10:e0126505.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Flores-Martínez SE, Castro-Martínez AG, López-Quintero A, García-Zapién AG, Torres-Rodríguez RN, Sánchez-Corona J. Association analysis of SNP-63 and indel-19 variant in the calpain-10 gene with polycystic ovary syndrome in women of reproductive age. Cir Cir. 2015;83:35–42.

    Article  PubMed  Google Scholar 

  26. Dadachanji R, Shaikh N, Khavale S, Patil A, Shah N, Mukherjee S. PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome. Fertil Steril. 2015;104:207–16.

    Article  PubMed  CAS  Google Scholar 

  27. Bass NM, Manning JA. Tissue expression of three structurally different fatty acid binding proteins from rat heart muscle, liver, and intestine. Biochem Biophys Res Commun. 1986;137:929–35.

    Article  PubMed  CAS  Google Scholar 

  28. Antonenkov VD, Sormunen RT, Ohlmeier S, Amery L, Fransen M, Mannaerts GP, et al. Localization of a portion of the liver isoform of fatty-acid-binding protein (L-FABP) to peroxisomes. Biochem J. 2006;394:475–84.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Guilmeau S, Niot I, Laigneau JP, Devaud H, Petit V, Brousse N, et al. Decreased expression of Intestinal I- and L-FABP levels in rare human genetic lipid malabsorption syndromes. Histochem Cell Biol. 2007;128:115–23.

    Article  PubMed  CAS  Google Scholar 

  30. Adida A, Spener F. Intracellular lipid binding proteins and nuclear receptors involved in branched-chain fatty acid signaling. Prostaglandins Leukot Essent Fat Acids. 2002;67:91–8.

    Article  CAS  Google Scholar 

  31. Gao N, Qu X, Yan J, Huang Q, Yuan HY, Ouyang DS. L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP. Mol Cell Biochem. 2010;345:207–14.

    Article  PubMed  CAS  Google Scholar 

  32. Francis GA, Fayard E, Picard F, Auwerx J. Nuclear receptors and the control of metabolism. Annu Rev Physiol. 2003;65:261–311.

    Article  PubMed  CAS  Google Scholar 

  33. Djouadi F, Weinheimer CJ, Saffitz JE, Pitchford C, Bastin J, Gonzalez FJ, et al. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator- activated receptor alpha-deficient mice. J Clin Invest. 1998;102:1083–91.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Fisher E, Weikert C, Klapper M, Lindner I, Möhlig M, Spranger J, et al. L-FABP T94A is associated with fasting triglycerides and LDL-cholesterol in women. Mol Genet Metab. 2007;91:278–84.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 program) (2012CB944700 and 2011CB944502) and the Science Research Foundation Item of No-Earnings Health Vocation (201002013). We also acknowledge Li You, Yuehong Bian, Changming Zhang, Guangyu Li, and Yongzhi Cao for specimen collection and technology support.

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Authors and Affiliations

  1. Center for Reproductive Medicine, Shandong Provincial Hospital affiliated to Shandong University, Shandong Provincial Key Laboratory of Reproductive Medicine, 324 Jingwu Road, Jinan, 250021, China

    Hongxi Xue, Han Zhao, Xin Liu, Yue-ran Zhao, Zi-Jiang Chen & Jinlong Ma

  2. Department of Reproductive Medicine, Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, China

    Hongxi Xue

  3. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China

    Hongxi Xue, Han Zhao, Xin Liu, Yue-ran Zhao, Zi-Jiang Chen & Jinlong Ma

  4. The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China

    Hongxi Xue, Han Zhao, Xin Liu, Yue-ran Zhao, Zi-Jiang Chen & Jinlong Ma

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  1. Hongxi Xue
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  2. Han Zhao
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  3. Xin Liu
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  4. Yue-ran Zhao
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Corresponding author

Correspondence to Jinlong Ma.

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Ethics statement

Written informed consent was obtained from all subjects. The study was approved by the Institutional Review Board at the Reproductive Hospital affiliated to Shandong University.

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The authors declare that they have no competing interests.

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Capsule

Analysis of FABP1 gene identified rs2197076 and rs2241883 polymorphisms involved in the pathogenesis of polycystic ovary syndrome in Chinese women.

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Xue, H., Zhao, H., Liu, X. et al. Association of single-nucleotide polymorphisms rs2197076 and rs2241883 of FABP1 gene with polycystic ovary syndrome. J Assist Reprod Genet 33, 75–83 (2016). https://doi.org/10.1007/s10815-015-0626-8

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  • DOI: https://doi.org/10.1007/s10815-015-0626-8

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