The prevalence of aortic calcification in Japanese compared to white and Japanese-American middle-aged men is confounded by the amount of cigarette smokingEl-Saed A, Curb JD, Kadowaki T, Okamura T, Sutton-Tyrrell K, Masaki K, Seto TB, Takamiya T, Choo J, Edmundowicz D, Evans RW, Fujiyoshi A, Nakamura Y, Miura K, Shin C, Kuller LH, Ueshima H, Sekikawa A.
Background: The prevalence of coronary artery calcification (CAC) in Japanese men is lower than in white and Japanese-American men. It is unclear if aortic calcification (AC) strongly linked to smoking is also lower in Japanese men who have many times higher smoking prevalence compared to US men. Methods: We conducted a population-based study of 903 randomly-selected men aged 40–49 years: 310 Japanese men in Kusatsu, Japan, 301 white men in Allegheny County, US, and 292 Japanese men in Hawaii, US (2002–2006). The presence of AC was assessed by electron-beam tomography. AC was defined as Agatston aortic calcium scores (AoCaS) >0 and ≥100. Results: Japanese (35.8%) had significantly less AoCaS>0 compared to both white (68.8%, pb0.001) and Japanese-American (62.3%, pb0.001) but similar AoCaS≥100 (19.4%, 18.3%, 22.6%, respectively, p=0.392). The pack-years of smoking, which was highest in Japanese, was the most important single associate of AC in all populations. Additionally age, low-density-lipoprotein cholesterol (LDL-C), and triglycerides in Japanese; body-mass index (BMI) in white; and BMI, LDL-C, hypertension, diabetes, and lipid medications in Japanese-American were independent associates of AC. The risk of AC using either cut points adjusted for pack-years of smoking and additional risk factors was lower in Japanese compared to both white and Japanese-American. AC and CAC had moderately positive and significant correlations in Japanese (r=0.26), white (r=0.39), and Japanese-American (r=0.45). Conclusions: The prevalence of AC defined both >0 and ≥100 was significantly lower in Japanese than in white and Japanese-American men after adjusting for cigarette smoking and additional risk factors.
Int J Cardiol. 2013 Jul 15;167(1):134-9. PMID: 22240754
Ethnic difference in liver fat content: A cross-sectional observation among Japanese American in Hawaii, Japanese in Japan, and non-Hispanic whites in United StatesAzuma K, Curb JD, Kadowaki T, Edmundowicz D, Kadowaki S, Masaki KH, El-Saed A, Nishio Y, Seto TB, Okamura T, Cetinel C, Kadota A, Sutton-Tyrrell K, Miura K, Evans RW, Takamiya T, Maegawa H, Miljkovic I, Kuller LH, Ueshima H, Kelley DE, Sekikawa A
BACKGROUND: We recently reported that Japanese had higher liver fat at a lower level of BMI compared with non-Hispanic whites (NHW). Objective: We hypothesize that ethnic difference in fat storage capacity contributes to this ethnic difference in liver fat. DESIGN: To examine this, we assessed liver fat among 244 Japanese-American aged 40-49, using regional computed-tomography images, along with metabolic variables. RESULTS: Despite the similar BMI between Japanese-Americans and NHW men, Japanese-Americans had more liver fat (liver to spleen attenuation ratio: 1.03 ± 0.22 for Japanese-Americans, and 1.07 ± 0.15 for NHW men; p < 0.05) and tended to have a greater disposition for fatty liver with an increase in BMI than NHW, indicating a clear difference between the two groups. In addition, liver fat is less in Japanese-Americans compared with Japanese men (1.03 ± 0.22 vs. 1.01 ± 0.16; p < 0.05), despite of a much higher BMI. These ethnic differences support the hypothesis that higher fat storage capacity indeed seems to be associated with less liver fat. In all the groups, liver fat content strongly correlated with triglycerides, homeostasis model assessment-insulin resistance, and C-reactive protein (CRP). Nevertheless, these metabolic variables were worse in Japanese-Americans, despite of less liver fat, compared with Japanese. Moreover, CRP levels were least among Japanese with highest liver fat, and highest among NHW men with least liver fat, despite of a strong positive association between CRP and fatty liver within each population. CONCLUSIONS: Fat content in the liver is intermediate for Japanese-Americans compared with Japanese and NHW men, which supports the hypothesis of less fat storage capacity among Japanese, closely linked to ethnic difference in predisposition to fatty liver.
Obes Res Clin Pract. 2013 May-Jun;7(3):e198-205. PMID: 23697588
Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson diseaseMilber JM, Noorigian JV, Morley JF, Petrovitch H, White L, Ross GW, Duda JE
Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.
Neurology. 2012 Dec 11;79(24):2307-14. doi: 10.1212. PMID: 23152586
FOXO3 gene variants and human aging: coding variants may not be key playersDonlon TA, Curb JD, He Q, Grove JS, Masaki KH, Rodriguez B, Elliott A, Willcox DC, Willcox BJ
FOXO3 is generally recognized as a “master” gene in aging since its association with longevity has been replicated in multiple organisms and human populations. A group of single nucleotide polymorphisms in linkage disequilibrium with a coding region has been associated with human longevity, but the actual functional variant is unidentified. Therefore, we sequenced the coding region in our long-lived Japanese American population in order to enhance resources for fine mapping this region. We demonstrate that of 38 published variants, 6 are misalignments with homologous nonallelic sequences from FOXO3B (ZNF286B), a pseudogene on a different chromosome; 2 are attributable to ZNF286B only, and the remaining 30 were unconfirmed, indicating that they are very rare and not likely involved in longevity. Furthermore, we identified a novel, unique, nonsynonymous coding variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic groups but appeared too rare for major longevity effects in our study populations.
J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1132-9. doi: 10.1093/gerona/gls067. Epub 2012 Mar 28. PMID: 22459618
Modeling regional vulnerability to Alzheimer pathologyRoyall DR, Palmer RF, Petrovitch H, Ross GW, Masaki K, White LR
Latent growth curve (LGC) models estimate change over time in a cohort's serially obtained measurements. We have applied LGC techniques to a spatial distribution of Alzheimer's disease (AD) pathology using autopsy data from 435 participants in the Honolulu-Asia Aging Study. Neurofibrillary tangle (NFT) and neuritic plaques (NP) were distributed across differently ordered sets of anatomical regions. The gradient of spatial change in neuritic plaque (dNP), was significantly associated with that of neurofibrillary tangle (dNFT), but weakly and inversely (r = -0.12; p < 0.001). Both dNFT and dNP correlated significantly and inversely with Braak stage. Sixty-one percent of the variance in Braak stage was explained by dNFT independent of covariates. Only dNFT was significantly associated with longitudinal change in cognition. Only dNP was associated with apolipoprotein (APOE) e4 burden. This is the first application of LGC models to spatially-ordered data. The result is a quantification of the interindividual variation in the interregional vulnerability to Alzheimer's disease lesions.
Neurobiol Aging. 2012 Aug;33(8):1556-63. doi: 10.1016/j.neurobiolaging.2011.05.028. Epub 2011 Jul 30. PMID: 21803455
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