Interactions between metallopeptidase 3 polymorphism rs679620 and BMI in predicting blood pressure in African-American women with hypertension.
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.
Taylor
Jacquelyn
J
Yale University, School of Nursing, New Haven, CT 06536, USA. Jacquelyn.taylor@yale.edu
Sun
Yan V
YV
Chu
Jian
J
Mosley
Thomas H
TH
Kardia
Sharon L
SL
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D005260:Female; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008019:Life Style; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012727:Sex Characteristics
D019278:Matrix Metalloproteinase 3