- Email: [email protected]
Genetic determinants of bp response to dash dietary patterns
76A
ASH XV ABSTRACTS
D009 ASSOCIATION OF I/D POLYMORPHYISM OF ANGIOTENSIN-I-CONVERTING ENZYME GENE IN POSTINFLUENZA PNEUMONIA IN ELDERLY SUBJECTS M. Onishi, S. Morimoto, K. Okaishi, S. Yoh, N. Fujiwara, T. Onishi, T. Ogihara. Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan. Postinfluenza pneumonia is one of the most serious problems for elder people. One of the main causes for the postinfluenza pneumonia is difficulty in discharge of sputum due to age-related decrease in cough reflex (Postgrad med J 72:343, 1996). In the present study, we investigated possible association of genetic polymorphisms of genes for coughrelated factors including angiotensin I-conveting enzyme (ACE) (I/D), angiotensinogen (M/T), angiotensin II type-1 receptor (A/C), and chymase (A/B), as well as in already known clinical risk factors, in a cohort study of 756 elderly subject aged 65 year and greater (mean age ⫾ SD age of 83 ⫾ 7 years) in a long-term care hospital. Elderly subjects with vaccination, with tube nutrition, or with ACE inhibitor administration were not included from the original. Out of the 756 elderly subject, 241 (43 males and 198 females) were suffered from influenza in the winter 1998/99, and 58 were suffered from postinfluenza pneumonia (ICD-9-CM criteria). Factors more often (p ⬍ 0.2) observed in the 58 patients with postinfluenza pneumonia compared to the 183 flu patients without pneumonia by univariate analyses were ACE I/D polymorphism (p ⫽ 0.002) asthma (0.003), ischemic heart disease (0.003), male gender (0.067), diabetes mellitus (0.094), dementia (0.105), renal failure (0.132), and past history of pneumonia (0.183). After adjustment by these confounding factors, logistic regression analysis revealed that ACE I/D polymorphism is a significantly participating risk for pneumonia in elderly patients with flu. Elderly subjects with DD genotype were significantly more susceptible for pneumonia than those with ID (RR ⫽ 3.0, p ⫽ 0.008) and those with II (RR ⫽ 5.5, p ⫽ 0.0005) in the flu patients. These findings indicate that genetic variants of ACE may be one source of genetic risk for influenza and have a benefit effect for prevention among elderly inpatients. Key Words: Postinfluenza pneumonia; insertion/deletion polymorphism of angiotensin I-converting enzyme gene; elderly subjects D010 GENETIC DETERMINANTS OF BP RESPONSE TO DASH DIETARY PATTERNS L.P. Svetkey*, T.J. Moore, F.M. Sacks, L.J. Appel*, D. SimonsMorton, G.A. Bray, P.R. Conlin, R. Mortensen, S.R. Mitchell. DASH Collaborative Research Group We hypothesized that the M235T polymorphism of the angiotensinogen gene (ANG) is associated with BP response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. These patterns included a control diet, similar to typical American intake; a “fruits and vegetables” diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and a “combination” diet (COMBO) that is reduced in fats and emphasizes fruits,
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
vegetables and low-fat dairy products. Sodium intake was not reduced and weight was held constant. In 355 of 459 DASH participants DNA was extracted from whole blood and genotyped at ANG. BP reduction was greatest in persons with the TT ANG genotype and least in those with the MM genotype (p for trend ⫽ .02 for both SBP and DBP) (Figure). Similar results have been reported for BP effects of sodium reduction weight loss. These data suggest that ANG genotype influences BP response to the DASH F/V and COMBO dietary patterns.
Key Words: Angiotensinogen gene; DASH diet; dietary patterns; genetics D011 THE ASSOCIATION OF 〉-T594M VARIANT IN THE AMILORIDE SENSITIVE SODIUM CHANNEL WITH END STAGE RENAL DISEASE Y.R. Su*1, M.C. Reif*1, Y. Cui1, L. Hiremath2, L. Hebert2, J. Eckfeldt3,4, D. Arnett3,4, M. Layne1, V. Carter*1, R.Y.K. Pun1 and A.G. Menon1. University of Cincinnati Medical Center, Cincinnati, OH1, Ohio State University, Columbus, OH2, University of Minnesota, MN3 and the HyperGEN consortium4. We have previously reported the identification of a variant (T594M) in the -subunit of the amiloride-sensitive sodium channel that occurs exclusively in the African American population (Su et al., 1996, J. Am. Soc. Nephrol., 7:2543– 2549). Lymphocytes from individuals with this mutant channel show increased sodium conductance in response to cAMP and loss of protein kinase C inhibition (Cui et al., 1997, PNAS 94:9962– 6). Association of the -T594M polymorphism with hypertension has been reported in blacks in London (Baker et al., 1998, Lancet 9:1388 –92). We screened 168 normotensive African American subjects and 844 hypertensive African American patients for the -T594M variant. In contrast to the study by Baker et al., we did not detect any significant difference in the allele frequency between the hypertensive and normotensive groups (0.036 and 0.037 respectively). However, the allele frequency in 205 patients with end stage renal disease (ESRD) was found to be higher (0.053) than the allele frequency in either the 168 normotensives or the 844 hypertensives on whom we had renal function data (p ⬍ 0.01). The higher allele frequency in ESRD was the same in patients with or without diabetes mellitus. Our results suggest that the -T594M variant may be associated with ESRD in African Americans.
ASH XV ABSTRACTS
D009 ASSOCIATION OF I/D POLYMORPHYISM OF ANGIOTENSIN-I-CONVERTING ENZYME GENE IN POSTINFLUENZA PNEUMONIA IN ELDERLY SUBJECTS M. Onishi, S. Morimoto, K. Okaishi, S. Yoh, N. Fujiwara, T. Onishi, T. Ogihara. Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan. Postinfluenza pneumonia is one of the most serious problems for elder people. One of the main causes for the postinfluenza pneumonia is difficulty in discharge of sputum due to age-related decrease in cough reflex (Postgrad med J 72:343, 1996). In the present study, we investigated possible association of genetic polymorphisms of genes for coughrelated factors including angiotensin I-conveting enzyme (ACE) (I/D), angiotensinogen (M/T), angiotensin II type-1 receptor (A/C), and chymase (A/B), as well as in already known clinical risk factors, in a cohort study of 756 elderly subject aged 65 year and greater (mean age ⫾ SD age of 83 ⫾ 7 years) in a long-term care hospital. Elderly subjects with vaccination, with tube nutrition, or with ACE inhibitor administration were not included from the original. Out of the 756 elderly subject, 241 (43 males and 198 females) were suffered from influenza in the winter 1998/99, and 58 were suffered from postinfluenza pneumonia (ICD-9-CM criteria). Factors more often (p ⬍ 0.2) observed in the 58 patients with postinfluenza pneumonia compared to the 183 flu patients without pneumonia by univariate analyses were ACE I/D polymorphism (p ⫽ 0.002) asthma (0.003), ischemic heart disease (0.003), male gender (0.067), diabetes mellitus (0.094), dementia (0.105), renal failure (0.132), and past history of pneumonia (0.183). After adjustment by these confounding factors, logistic regression analysis revealed that ACE I/D polymorphism is a significantly participating risk for pneumonia in elderly patients with flu. Elderly subjects with DD genotype were significantly more susceptible for pneumonia than those with ID (RR ⫽ 3.0, p ⫽ 0.008) and those with II (RR ⫽ 5.5, p ⫽ 0.0005) in the flu patients. These findings indicate that genetic variants of ACE may be one source of genetic risk for influenza and have a benefit effect for prevention among elderly inpatients. Key Words: Postinfluenza pneumonia; insertion/deletion polymorphism of angiotensin I-converting enzyme gene; elderly subjects D010 GENETIC DETERMINANTS OF BP RESPONSE TO DASH DIETARY PATTERNS L.P. Svetkey*, T.J. Moore, F.M. Sacks, L.J. Appel*, D. SimonsMorton, G.A. Bray, P.R. Conlin, R. Mortensen, S.R. Mitchell. DASH Collaborative Research Group We hypothesized that the M235T polymorphism of the angiotensinogen gene (ANG) is associated with BP response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. These patterns included a control diet, similar to typical American intake; a “fruits and vegetables” diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and a “combination” diet (COMBO) that is reduced in fats and emphasizes fruits,
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
vegetables and low-fat dairy products. Sodium intake was not reduced and weight was held constant. In 355 of 459 DASH participants DNA was extracted from whole blood and genotyped at ANG. BP reduction was greatest in persons with the TT ANG genotype and least in those with the MM genotype (p for trend ⫽ .02 for both SBP and DBP) (Figure). Similar results have been reported for BP effects of sodium reduction weight loss. These data suggest that ANG genotype influences BP response to the DASH F/V and COMBO dietary patterns.
Key Words: Angiotensinogen gene; DASH diet; dietary patterns; genetics D011 THE ASSOCIATION OF 〉-T594M VARIANT IN THE AMILORIDE SENSITIVE SODIUM CHANNEL WITH END STAGE RENAL DISEASE Y.R. Su*1, M.C. Reif*1, Y. Cui1, L. Hiremath2, L. Hebert2, J. Eckfeldt3,4, D. Arnett3,4, M. Layne1, V. Carter*1, R.Y.K. Pun1 and A.G. Menon1. University of Cincinnati Medical Center, Cincinnati, OH1, Ohio State University, Columbus, OH2, University of Minnesota, MN3 and the HyperGEN consortium4. We have previously reported the identification of a variant (T594M) in the -subunit of the amiloride-sensitive sodium channel that occurs exclusively in the African American population (Su et al., 1996, J. Am. Soc. Nephrol., 7:2543– 2549). Lymphocytes from individuals with this mutant channel show increased sodium conductance in response to cAMP and loss of protein kinase C inhibition (Cui et al., 1997, PNAS 94:9962– 6). Association of the -T594M polymorphism with hypertension has been reported in blacks in London (Baker et al., 1998, Lancet 9:1388 –92). We screened 168 normotensive African American subjects and 844 hypertensive African American patients for the -T594M variant. In contrast to the study by Baker et al., we did not detect any significant difference in the allele frequency between the hypertensive and normotensive groups (0.036 and 0.037 respectively). However, the allele frequency in 205 patients with end stage renal disease (ESRD) was found to be higher (0.053) than the allele frequency in either the 168 normotensives or the 844 hypertensives on whom we had renal function data (p ⬍ 0.01). The higher allele frequency in ESRD was the same in patients with or without diabetes mellitus. Our results suggest that the -T594M variant may be associated with ESRD in African Americans.