The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

R Miller, R Smiley, E A Thom, W A Grobman, J D Iams, B M Mercer, G Saade, A T Tita, U M Reddy, D J Rouse, Y Sorokin, S C Blackwell, M S Esplin, J E Tolosa, S N Caritis

Journal: BJOG : an international journal of obstetrics and gynaecology 2015;122(10):1387-94

PMID: 25600430

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Abstract

OBJECTIVE

To determine whether β2 -adrenoceptor (β2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester.

DESIGN

A case-control ancillary study to a multicentre randomised controlled trial.

SETTING

Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

POPULATION

Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length.

METHODS

Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27.

MAIN OUTCOME MEASURES

Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks.

RESULTS

Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited.

CONCLUSIONS

β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway.

Address: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.; Division of Obstetrical Anesthesiology, Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.; The George Washington University Biostatistics Center, Washington, DC, USA.; Departments of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA.; The Ohio State University, Columbus, OH, USA.; Case Western Reserve University-MetroHealth Medical Center, Cleveland, OH, USA.; University of Texas Medical Branch, Galveston, TX, USA.; University of Alabama at Birmingham, Birmingham, AL, USA.; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.; Brown University, Providence, RI, USA.; Wayne State University, Detroit, MI, USA.; The University of Texas Health Science Center at Houston-Children's Memorial Hermann Hospital, Houston, TX, USA.; University of Utah Health Sciences Center, Salt Lake City, UT, USA.; Oregon Health and Science University, Portland, OR, USA.; University of Pittsburgh, Pittsburgh, PA, USA.

DOI: 10.1111/1471-0528.13243

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MeSH Terms: Adult, Case-Control Studies, Cervical Length Measurement, Female, Genetic Markers, Genotype, Homozygote, Humans, Polymorphism, Single Nucleotide, Pregnancy, Pregnancy Trimester, Second, Premature Birth, Prospective Studies, Receptors, Adrenergic, beta-2, Uterine Cervical Incompetence