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Polymorphisms Within the Interleukin-1ß Gene Cluster and Preeclampsia

From the Departments of Obstetrics and Gynecology and Molecular Human Genetics, Baylor College of Medicine, Houston, Texas.

Address reprint requests to: Anthony R. Gregg, MD Department of Obstetrics and Gynecology Baylor College of Medicine 6550 Fannin, Suite 901 Houston, TX 77030 E-mail: agregg{at}bcm.tmc.edu

Objective: To identify associations between polymorphisms within the interleukin-1ß gene cluster, all of which increase protein expression, and preeclampsia.

Methods: We genotyped a Hispanic population (69 women with preeclampsia and 47 controls) for two polymorphisms of the interleukin-1ß gene (promoter region and exon 5) and one polymorphism of the interleukin-1 receptor antagonist gene in intron 2. Clinical data were collected from medical records. Values are given as means or medians. Statistical power to identify a difference in occurrence of interleukin-1ß promoter, interleukin-1ß exon 5, and interleukin-1 receptor antagonist gene polymorphisms in women with preeclampsia compared with controls was 21%, 15.9%, and 30.9%, respectively.

Results: We found no association between any single polymorphism and occurrence of preeclampsia. Among women with preeclampsia, those with polymorphism of interleukin-1 receptor antagonist gene had higher mean systolic blood pressure (BP) at admission (178 ± 33.4 versus 159 ± 19.5 mmHg, P = .039). When all three polymorphisms combined were evaluated, women with preeclampsia and at least three mutant alleles (n = 8) had higher mean systolic BP at admission (182 ± 30 versus 160 ± 20.5 mmHg, P = .009) and increased alanine aminotransferase (67 [10–1024] versus 20 [3–407] IU/L, P = .04) and aspartate aminotransferase (119 [25–2239] versus 24 [4–489] IU/L, P = .002). At admission, BP in controls was independent of any polymorphism identified.

Conclusion: Although the power of this study was limited, our data do not support a role for polymorphisms of the interleukin-1ß and interleukin-1 receptor antagonist genes in the pathogenesis of preeclampsia among Hispanic women. Our findings do suggest that polymorphisms within the gene cluster might influence severity of preeclampsia.

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