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Ethnic Differences of Polymorphisms in Cytokine and Innate Immune System Genes in Pregnant Women

Daniel P. Nguyen, MD^*, Mehmet Genc, MD, PhD^*, Santosh Vardhana^*, Oksana Babula, MD^*, Andrew Onderdonk, PhD and Steven S. Witkin, PhD^*

From the *Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, New York; and Department of Obstetrics, Gynecology and Reproductive Biology and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Address reprint requests to: Dr. Steven S. Witkin, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 525 East 68th Street, Box 35, New York, NY 10021; e-mail: switkin{at}med.cornell.edu.

OBJECTIVE: Investigations of the possible role of polymorphic genes in pregnancy outcome may be influenced by ethnic variations in genotype or allele frequencies. Differences in allelic carriage of immune system-related genes among white, black, and Hispanic pregnant women living in New York City and Boston were evaluated.

METHODS: DNA was extracted from buccal or vaginal epithelial cells collected from 198 white, 75 black, and 114 Hispanic pregnant women who delivered at term and who had no history of a preterm birth. Genetic polymorphisms in the immunoregulatory genes encoding interleukin (IL)-1ß, tumor necrosis factor-, IL-4, IL-10, IL-1 receptor antagonist (IL-1ra), mannose-binding lectin, toll-like receptor-4, and the 70-kDa heat shock protein were determined.

RESULTS: Allele 2 of the IL-1ra gene (IL1RN*2) and IL-4 –590C homozygosity were 4-fold less common in blacks than in whites or Hispanics (P < .001). The IL-4 –590T allele was almost 2-fold more common in Hispanics than in whites (P < .001). The frequency of the 70-kDa heat shock protein 1267G allele was at least 1.4 times greater in blacks compared with whites (P < .001) or Hispanics (P = .002), whereas the homozygous mannose-binding lectin codon 54G allele was observed at least 4.5 times more often in Hispanics compared with whites (P = .007) or blacks (P = .02).

CONCLUSION: Investigations of the role of genetic factors affecting pregnancy outcome must be cognizant of ethnic variations when enrolling case and control subjects for studies on allele and genotype frequencies.

LEVEL OF EVIDENCE: III

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