Do long-term HDL-C declines associated with a first birth vary by apo E phenotype? The Coronary Artery Risk Development in Young Adults (CARDIA) study.
BACKGROUND
High-density lipoprotein cholesterol (HDL-C) levels in premenopausal and postmenopausal women are differentially affected by exogenous sex hormones depending on their apolipoprotein E (apo E) genotype. Because endogenous sex hormones markedly increase during pregnancy, we examined whether HDL-C declines after a first birth varied by apo E polymorphisms.


METHODS
In 1147 nulliparas (416 black, 731 white), fasting blood samples (nonpregnant) were drawn at baseline and at follow-up years 5, 7, and 10. Time-dependent pregnancy groups included 0 pregnancies (P0), 1+ short pregnancy (P1+), 1 birth (B1), 2 or more births (B2+). ApoE groups by alleles identified with a phenotype method included E4 (4/3 and 4/4), E3 (3/3), and E2 (2/2 and 3/2). Differences in adjusted mean HDL-C changes among pregnancy groups and ApoE groups were examined using repeated measures multiple linear regression.


RESULTS
HDL-C declines associated with parity (one or more births) depended on ApoE group (ApoE*Pregnancy Interaction; p < 0.002). For B1 and B2+ vs. P0, HDL-C declines were -2.4 to -2.7 mg/dl in E4 and -3.4 to -4.1 mg/dl in E3. In E2, HDL-C declines were -6.6 mg/dl for one birth, and -11.5 mg/dl for two or more births, each relative to the 0 pregnancies (P0) group (linear trend, p < 0.001).


CONCLUSIONS
The degree to which childbearing adversely affects long-term HDL-C declines varies by apo E phenotype, based on a method that accurately classifies genotype. Our findings show that 2/2 and 3/2 genotypes are associated with larger parity-related HDL-C declines than 3/3, 4/3, and 4/4 genotypes.
Gunderson
Erica P
EP
Kaiser Permanente Division of Research, Etiology and Prevention, Kaiser Permanente, Oakland, California 94612, USA. epg@dor.kaiser.org
Whitmer
Rachel A
RA
Lewis
Cora E
CE
Quesenberry
Charles P
CP
West
Delia Smith
DS
Sidney
Stephen
S
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D010298:Parity / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D044465:White People / Q000235:genetics; D016387:Women's Health
D001057:Apolipoproteins E; D008076:Cholesterol, HDL