Abstract P271: Association Between Nitric Oxide Synthase Gene Polymorphism ( Glu298Asp ) and Blood Pressure in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: Endothelial NO synthase ( eNOS ) gene polymorphism at position 894 (G>T, Glu298Asp ) resulting in a T allele is related to higher blood pressure (BP) levels, but the association of Glu298Asp and temporal increase in BP in adulthood has not been studied, nor is it known whether the association between Glu298Asp and BP is modified by habitual intake of fruits and vegetables, an abundant source of nitrate for conversion to NO. Hypothesis: We hypothesized that homozygous (TT) or heterozygous genotype (GT) status of Glu298Asp is associated with BP increase over a course of 9 years among black and white adults, compared to normal genotype (GG). Further, the association is amplified by higher habitual intake of fruits and vegetables. Methods: Among 9488 white (mean age: 54.3 years, 47.0% men) and 2861 black members of the ARIC cohort (mean age: 53.4 years, 37.2% men) at baseline (1987-1989), genotyping of the NOS3 Glu298Asp polymorphism (rs1799983) was conducted using the TaqMan assay (Applied Biosystems, Foster City, CA, USA). The rs1799983 levels 1.5-2, 0.5-1.49, <0.5 were categorized as TT, GT, GG, respectively. We used the average of repeated sitting blood pressure at 4 cohort examinations through 1996-1998. Average intake of vegetables and fruit was calculated from food frequency questionnaires at exams 1 and 3, and analyzed as quartiles. A diet score without fruit and vegetables intake was created using principal component analysis. Mixed models were used to estimate the association between NOS3 G894T (TT or GT vs. GG) with level and change of SBP and DBP, adjusting for age, sex, genotypes, BMI, smoking status, diabetes, and physical activity. The analysis was also conducted within each quartile of vegetables and fruit intake, with further adjustment for the diet score without fruit and vegetables intake. Results: The genotypes of TT, GT and GG of Glu298Asp were present in 800 (8.4%), 4057 (42.8%), 4631 (48.8%) white participants, and 26 (0.9%), 510 (17.8%), 2335 (81.3%) black participants. Among whites with the genotype GT/TT, DBP increased 2.46 mmHg (95% CI: 0.02, 4.90) over 9 years compared to GG participants. The interaction between Glu298Asp and intake of fruit and vegetables was not statistically significant. There was no statistically significant association between GT/TT and SBP, nor with 9-year change of SBP or DBP among black participants. Conclusion: Carrier status of the GT/TT genotypes of Glu298Asp is associated with higher level of DBP among white adults, but not with SBP over a course of 9 years compared to the GG genotype of Glu298Asp . There is no interaction found between Glu298Asp and intake of fruit and vegetables in association with SBP or DBP.