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Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Buxbaum, J, Alexander, A, Koziol, J, Tagoe, C, Fox, E, Kitzman, D |
| Journal | Am Heart J |
| Volume | 159 |
| Issue | 5 |
| Pagination | 864-70 |
| Date Published | 2010 May |
| ISSN | 1097-6744 |
| Keywords | Adult, African Americans, Aged, Aged, 80 and over, Amyloidosis, Female, Gene Frequency, Heart Diseases, Humans, Isoleucine, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Prealbumin, Ultrasonography, Valine |
| Abstract | <p><b>BACKGROUND: </b>Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the allele frequency and its clinical penetrance in community-dwelling African Americans.</p><p><b>METHODS: </b>Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls.</p><p><b>RESULTS: </b>One hundred nineteen (3.23%) of 3,712 ARIC and 17 (2.12%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38% vs 15%, relative risk 2.62, P = .04) and mortality (76% vs 53%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender- and ethnically matched controls. In ARIC (all subjects <65 years old), there were no differences between carriers and noncarriers in mortality, frequency of congestive heart failure, or findings consistent with cardiac amyloidosis.</p><p><b>CONCLUSIONS: </b>Heterozygosity for the amyloidogenic TTR V122I mutation is relatively common in community-dwelling African Americans. Before the age of 65 years, the allele has no discernible impact on cardiac function or mortality. After the age of 70 years, carriers show a higher frequency of congestive failure and greater mortality with more echocardiographic evidence suggestive of cardiac amyloidosis, findings consistent with age-dependent clinical penetrance of this autosomal dominant gene.</p> |
| DOI | 10.1016/j.ahj.2010.02.006 |
| Alternate Journal | Am. Heart J. |
| PubMed ID | 20435197 |
| PubMed Central ID | PMC2865207 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01 HC055022 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States U01 HL080295-05 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States R37 AG018915 / AG / NIA NIH HHS / United States R01 AG018915 / AG / NIA NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States R01 AG019259-07 / AG / NIA NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States N01 HC055021 / HC / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 AG019259 / AG / NIA NIH HHS / United States N01 HC055020 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States |