Effect of pregnancy-associated plasma protein-A (PAPP-A) single-nucleotide polymorphisms on the level and activity of PAPP-A and the hormone profile in fluid from normal human small antral follicles

The 1224 single-nucleotide polymorphism genotype of pregnancy-associated plasma protein-A (PAPP-A) correlates with the PAPP-A level and activity in normal human small antral follicles.

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Volume 106, Issue 7, Pages 1778-1786

Authors:

Jane Alrø Bøtkjær, M.Sc., Tanni Borgbo, Ph.D., Søren Kløverpris, Ph.D., Pernille Rimmer Noer, M.Sc., Claus Oxvig, Ph.D., Claus Yding Andersen, D.M.Sc.

Abstract:

Objective

To reveal a possible relationship between two single nucleotide polymorphisms (SNPs) in PAPP-A—1224 (rs7020782) and 327 (rs12375498)—and the level and activity of PAPP-A in follicular fluid (FF) of human small antral follicles, and to analyze the intrafollicular hormone levels.

Design

Laboratory investigation.

Setting

University hospital.

Patient(s)

Fifty volunteer women who contributed a total of 210 samples of FF from normal small antral follicles.

Intervention(s)

Genotyping and measurement of antigen levels of steroids, PAPP-A, stanniocalcin-2 (STC2), and antimüllerian hormone (AMH) plus activity of PAPP-A toward insulin-like growth factor binding protein 4 (IGFBP-4).

Main Outcome Measure(s)

Measurement of PAPP-A levels and hormones with enzyme-linked immunosorbent assay (ELISA) and PAPP-A activity toward radiolabeled IGFBP-4.

Result(s)

Women homozygous for the minor C allele of the 1224 SNP showed a statistically significantly lower level of PAPP-A protein and activity in FF compared with women carrying the major A allele. These women also displayed nonsignificant reduced levels of estradiol and increased levels of AMH and androgen. A statistically significant correlation between FF levels of PAPP-A activity and the molar ratio of PAPP-A/STC2 was obtained. The 327 SNP did not show statistically significant associations.

Conclusion(s)

This study presents a statistically significant effect of the 1224 SNP on the level and activity of PAPP-A in human follicles, suggesting that the FF level of bioactive insulin-like growth factor depends on the genotype. We observed STC2 to be an important regulator of PAPP-A in human FF. The 1224 SNP has previously been associated with recurrent pregnancy loss, so further evaluation of an underlying mechanism including aberrant control of insulin-like growth factor activity is warranted.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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