Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women

We investigated a biracial cohort of women at the end of their reproductive life. Carrying the apolipoprotein E*2 allele was a risk factor for pregnancy loss only in white women.


Silvia Gamundi-Segura, M.Sc., Elena Torres-Perez, M.Sc., Alejandro Sanz-Paris, M.D., Jose M. Arbones-Mainar, Ph.D.

Volume 105, Issue 6, Pages 1554-1560



To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations.


Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations.


Not applicable.


Women without miscarriages (controls) and women who miscarried at least once (cases).



Main Outcome Measure(s):

A group of women (n = 1,372) successfully followed for 25 years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk.


In white women followed up for 25 years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04–2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06–2.05).


This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.

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