2015.7.31Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels.
Setoh K, Terao C, Muro S, Kawaguchi T, Tabara Y, Takahashi M, Nakayama T, Kosugi S, Sekine A, Yamada R, Mishima M, Matsuda F.
Alpha-1 antitrypsin (AAT) encoded by SERPINA1 is an acute-phase inflammation marker, and AAT deficiency (AATD) is known as one of the common genetic disorders in European populations. However, no genetic determinants to AAT levels apart from the SERPINA gene clusters have been identified to date. Here we perform a genome-wide association study of serum AAT levels followed by a two-staged replication study recruiting a total of 9,359 Japanese community-dwelling population. Three missense variants of metabolic syndrome-related genes, namely, rs671 in ALDH2, rs1169288 in HNF1A and rs1260326 in GCKR, significantly associate with AAT levels (P≤1.5 × 10(-12)). Previous reports have shown the functional relevance of ALDH2 and HNF1A to AAT. We observe a significant interaction of rs671 and alcohol consumption on AAT levels. We confirm the association between AAT and rs2896268 in SERPINA1, which is independent of known causative variants of AATD. These findings would support various AAT functions including metabolic processes.
2015.2.15Central blood pressure relates more strongly to retinal arteriolar narrowing than brachial blood pressure: the Nagahama Study.
Kumagai K, Tabara Y, Yamashiro K, Miyake M, Akagi-Kurashige Y, Oishi M, Yoshikawa M, Kimura Y, Tsujikawa A, Takahashi Y, Setoh K, Kawaguchi T, Terao C, Yamada R, Kosugi S, Sekine A, Nakayama T, Matsuda F, Yoshimura N; Nagahama Study group.
OBJECTIVES: Although central blood pressure (BP) is considered to be more closely associated with large arterial remodeling and cardiovascular outcomes than brachial BP, few studies have investigated these associations with changes in small arteries. As morphological changes in retinal vessels might be associated with cardiovascular outcomes, we conducted a cross-sectional study to investigate the association of central BP with retinal vessel caliber.
METHODS: The study included 8054 Japanese participants. Central BP was estimated by the radial arterial waveform by calibrating brachial BP. Central retinal arteriolar equivalent (CRAE) was computationally measured using fundus photography.
RESULTS: CRAE was most strongly associated with central SBP (r = -0.324, P < 0.001), followed by DBP (r = -0.292, P < 0.001) and central pulse pressure (PP; r = -0.226, P < 0.001). The correlation coefficient between SBP and CRAE was significantly greater in central SBP than in brachial SBP (r = -0.300, P < 0.001). After adjustment for possible covariates, brachial SBP (β = -0.221, P < 0.001) and central SBP (β = -0.239, P < 0.001) were independently associated with CRAE. Further, higher brachial SBP (β = -0.226, P < 0.001) and smaller PP amplification (β = 0.092, P < 0.001) were identified as independent determinants of narrowing of CRAE in the same equation, which indicated the superiority of central BP. Central BP-determined hypertensive individuals had a significantly narrower CRAE independent of brachial BP (central/brachial: hypertension/hypertension 121.4 ± 11.5, hypertension/normotension 120.9 ± 11.2, normotension/hypertension 125.1 ± 11.9, normotension/normotension 128.1 ± 11.5 μm).
CONCLUSION: Central BP was more closely associated with the narrowing of CRAE than brachial BP. Slight increases in central BP might be involved in the morphological changes in small retinal arteries, even in individuals with optimal brachial BP.