As hypothesized, findings of the present study suggest some associations between genetic polymorphisms and environmental lifestyle variables on BP in African American mothers and daughters. Hunt et al. (2006)
have proposed that certain SNPs on SLC4A5
, while inconsistent in phenotypes, may compensate for abnormal NaHCO3
transporting by modifying other ion transporters. Furthermore, they questioned if it is these SNPs alone or in linkage disequilibrium with other SNPs that result in changes to Na and HCO3
transport. Hunt et al. found a significant relationship between SLC4A5
and BP in 96 Utah pedigrees, which is consistent with findings of the current study, in which SNP rs10177833 genotypes C/A and A/A on SLC4A5
have statistically significant associations with SBP (p
= .030 and p
= .046, respectively).
Although no significant main effects were found for sodium intake on BP, both SBP and DBP were slightly higher for the total sample of participants who consumed less than 2,300 mg/day of sodium than for people who consumed 2,300 mg/day or more (135 mmHg vs. 129 mmHg for SBP, and 83 mmHg vs. 80 mmHg for DBP, respectively, ). Similarly, Ajani, Dunbar, Ford, Mokdad, and Mensah (2005)
reported that participants with hypertension revealed a lower intake of dietary sodium than those with normal BP. This result may be due to the large variability of using a single 24-hr recall of dietary data. The true rate of sodium consumption may have been underestimated for this study population. Further, women who were diagnosed with hypertension may have received suggestions from physicians to reduce their consumption of sodium.
In the current study, surprisingly, participants with C/T genotype of rs8179526 who consumed the recommended 2,300 mg per day of sodium or more had lower SBP than those who consumed less than 2,300 mg per day. This finding is inconsistent with reports by the AHA (2005)
and Douglas et al. (2003)
that indicated that increases in dietary sodium are related to increases in SBP. Other studies have shown that high amounts of dietary sodium are a risk factor for hypertension among African Americans due to increased salt sensitivity in this population (Flack, 2003
). Flack et al (2002)
also indicated that women tend to be more salt sensitive than men. Given the findings of the present study and their inconsistency with previous studies, genetic counseling and rs8179526 genetic and urinary sodium sensitivity testing may be beneficial when treating and managing hypertension in African American women (Taylor & Wu, 2009
Women with the T/T genotype of rs8179526 who consumed more the recommended 2,300 mg of sodium or more per day had higher SBP readings than those who consumed less than 2,300 mg per day. Genotype T/T on rs8179526 thus resulted in a risk effect on SBP when participants reported higher than recommended intakes of sodium. These results indicate that there is a gene × environmental interaction with sodium intake on BP. However, these differences of BP may also be due to other environmental factors, such as physical activity, socioeconomic status, and social support (, ). No significant gene × sodium interaction was found on DBP for any of the four SNPs tested.
An additional finding is that exercising a minimum of 30 minutes per day was associated with lower SBP and DBP readings, though the differences were not statistically significant (). These findings are consistent with previous studies and the recommendations of JNC-7 (Chobanian et al., 2003
). Two statistically significant interactions of gene × physical activity on SBP were found on rs1017783l. Participants with C/A and A/A genotypes of rs1017783l showed increased SBP among those reporting less than 30minutes of physical activity per day while those with a C/C genotype and less than 30 minutes of physical activity per day reported had decreased SBP (, ). This pattern also was found with DBP on rs10177831. Participants with the A/A genotype of rs10177831 who reported less than 30 minutes of physical activity per day had statistically significantly increased DBP, while those with a C/C genotype had decreased DBP (, ). For rs6731545, two statistically significant interactions of gene × physical activity on both SBP and DBP were found. Participants with the G/A genotype reporting less than 30 minutes of physical activity per day had increased SBP and DBP, while no significant interactions were found with BP and physical activity for those with the G/G genotype (; and ).
Interaction of rs10177833 × physical activity status on systolic blood pressure (SBP). A = adenine; C = cytosine.
Interaction of rs10177833 × physical activity on diastolic blood pressure (DBP). A = adenine; C = cytosine.
Interaction of rs6731545 × physical activity on systolic blood pressure (SBP). A = adenine; G = guanine.
Several limitations of this study need to be considered. This study was restricted to African American women residing in a large urban metropolitan area. The results may, thus, not be generalizable to other ethnic groups or to those living in suburban or rural areas. Also, a single 24-hr food recall was used for sodium intake data. The reliability and validity of this method increases with the number of days of food recall and objective measures (e.g., urinary sodium). A 24-hr recall of dietary intake may result in a larger variability as a result of underestimation (e.g., could not eat too much because of illness) or overestimation (e.g., had eaten at a buffet before this interview) of sodium consumption in this population.
The approach for this study was based on the premise that susceptibility alleles for common diseases were not under strong negative selection, and common variants contributed to common disease traits (i.e., the common disease–common variant hypothesis; Reich & Lander, 2001
). However, the allelic spectrum for genes associated with complex quantitative traits, such as HBP, has not been fully delineated. It is possible that multiple rare polymorphisms in the biological and positional candidate genes that were not included in this study could influence HBP. Despite these limitations, the approach employed in the current study with an adequate sample size illustrates the use of SNPs in candidate genes to construct a more complete picture of the genetic architecture of complex traits such as HBP.
Clinically, the roles of rs8179526 and rs10177833 in African American mothers and daughters can be confusing. When patients with known risk factors such as high sodium intake are assessed, genotype can provide clues as to the appropriate treatment options for lowering BP. Clinicians should be aware of the gene-environment effects of rs8179526 and sodium intake when assessing and treating African American women and girls for HBP. These findings add to the body of evidence suggesting a role for rs8179526 and rs10177833 in HBP among African American females.
Nurses need to educate their African American female patients about the possibility of having an increased risk for developing HBP based on their individual genotypes. Modifying dietary sodium intake and physical activity routines can lower BP, but interventions should be based on the individual profile of the patient (i.e., genotype). If gene-environment screening occurs earlier in life, appropriate interventions can be implemented to reduce morbidity and mortality related to HBP. The next step in studying gene-environment interactions on HBP among African American parents and children could use a similar research design but incorporate a genome-wide association approach.