Dataset Information

Interactions between metallopeptidase 3 polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension.

ABSTRACT: BMI represents an internal metabolic and physiological environment that plays a key role in development of high blood pressure (BP) for many Americans. African-American women have a higher prevalence of high BP and being overweight than men or other ethnic groups. This study examines the genetic-environmental interaction effects of single nucleotide polymorphisms and BMI on BP among African-American women using 1418 African-American women and men from the Genetic Epidemiology Network of Arteriopathy study. A total of 403 tests of single nucleotide polymorphism-BMI interaction were conducted using methods of internal replication, cross-validation, and false discovery rate. One single nucleotide polymorphism (located in the ATP6B1 gene, rs2266917) passed adjustments for multiple testing and had a significant independent main effect (P = 0.0018) on diastolic BP among African-American women. A significant sex-specific interaction effect was found between MMP3_rs679620 and BMI in African-American women (P = 0.0009). MMP3_rs679620 (A-G polymorphism) encodes a Lys-Glu nonsynonymous variant at the 45th amino acid of metallopeptidase 3 and indicates a putative functional modification of metallopeptidase 3. These findings were not identified in African-American men. MMP3_rs679620 appears to have a protective effect on diastolic BP in women with high BMI. Surprisingly, MMP3_rs679620 had the opposite effect on women with low BMI, resulting in higher diastolic BP.

SUBMITTER: Taylor J

PROVIDER: S-EPMC3005718 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Interactions between metallopeptidase 3 polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension.

Taylor Jacquelyn J Sun Yan V YV Chu Jian J Mosley Thomas H TH Kardia Sharon L SL

Journal of hypertension 20081201 12

BMI represents an internal metabolic and physiological environment that plays a key role in development of high blood pressure (BP) for many Americans. African-American women have a higher prevalence of high BP and being overweight than men or other ethnic groups. This study examines the genetic-environmental interaction effects of single nucleotide polymorphisms and BMI on BP among African-American women using 1418 African-American women and men from the Genetic Epidemiology Network of Arteriop ...[more]

PMID: 19008710

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Project description:BackgroundTiming of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking.ObjectivesWe assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production.MethodsA candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1β production was quantified. Medical record review determined timing of birth.ResultsWomen with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1β production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05).DiscussionWomen with GG genotype may be at risk for earlier birth because of diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

Dataset Information

Interactions between metallopeptidase 3 polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension.

Publications

Interactions between metallopeptidase 3 polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension.

Similar Datasets

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