TY - JOUR
T1 - DNA methylation level of the gene encoding thioredoxin-interacting protein in peripheral blood cells is associated with metabolic syndrome in the Japanese general population
AU - Yamazaki, Mirai
AU - Yamada, Hiroya
AU - Munetsuna, Eiji
AU - Maeda, Keisuke
AU - Ando, Yoshitaka
AU - Mizuno, Genki
AU - Fujii, Ryosuke
AU - Tsuboi, Yoshiki
AU - Ohashi, Koji
AU - Ishikawa, Hiroaki
AU - Hashimoto, Shuji
AU - Hamajima, Nobuyuki
AU - Suzuki, Koji
N1 - Publisher Copyright:
© 2022 The Japan Endocrine Society.
PY - 2022
Y1 - 2022
N2 - Metabolic syndrome (MetS) is cluster of metabolic diseases, including abdominal obesity, hyperglycemia, high blood pressure, and dyslipidemia, that directly escalate the risk of type 2 diabetes, heart disease, and stroke. Thioredoxin-interacting protein (TXNIP) is a binding protein for thioredoxin, a molecule that is a key inhibitor of cellular oxidation, and thus regulates the cellular redox state. Epigenetic alteration of the TXNIP-encoding locus has been associated with components of MetS. In the present study, we sought to determine whether the level of TXNIP methylation in blood is associated with MetS in the general Japanese population. DNA was extracted from the peripheral blood cells of 37 subjects with and 392 subjects without MetS. The level of TXNIP methylation at cg19693031 was assessed by the bisulfitepyrosequencing method. We observed that TXNIP methylation levels were lower in MetS subjects (median 74.9%, range 71.7–78.4%) than in non-MetS subjects (median 77.7%, range 74.4–80.5%; p = 0.0024). Calculation of the confounding factor-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hypomethylation revealed that subjects with MetS exhibited significantly higher ORs for hypomethylation than did those without MetS (OR, 2.92; 95% CI, 1.33–6.62; p = 0.009). Our findings indicated that lower levels of TXNIP methylation are associated with MetS in the general Japanese population. Altered levels of DNA methylation in TXNIP at cg19693031 might play an important role in the pathogenesis of MetS.
AB - Metabolic syndrome (MetS) is cluster of metabolic diseases, including abdominal obesity, hyperglycemia, high blood pressure, and dyslipidemia, that directly escalate the risk of type 2 diabetes, heart disease, and stroke. Thioredoxin-interacting protein (TXNIP) is a binding protein for thioredoxin, a molecule that is a key inhibitor of cellular oxidation, and thus regulates the cellular redox state. Epigenetic alteration of the TXNIP-encoding locus has been associated with components of MetS. In the present study, we sought to determine whether the level of TXNIP methylation in blood is associated with MetS in the general Japanese population. DNA was extracted from the peripheral blood cells of 37 subjects with and 392 subjects without MetS. The level of TXNIP methylation at cg19693031 was assessed by the bisulfitepyrosequencing method. We observed that TXNIP methylation levels were lower in MetS subjects (median 74.9%, range 71.7–78.4%) than in non-MetS subjects (median 77.7%, range 74.4–80.5%; p = 0.0024). Calculation of the confounding factor-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hypomethylation revealed that subjects with MetS exhibited significantly higher ORs for hypomethylation than did those without MetS (OR, 2.92; 95% CI, 1.33–6.62; p = 0.009). Our findings indicated that lower levels of TXNIP methylation are associated with MetS in the general Japanese population. Altered levels of DNA methylation in TXNIP at cg19693031 might play an important role in the pathogenesis of MetS.
KW - DNA methylation
KW - Metabolic disorder
KW - Obesity
KW - Pyrosequencing
KW - Thioredoxin-interacting protein (TXNIP)
UR - http://www.scopus.com/inward/record.url?scp=85124746131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124746131&partnerID=8YFLogxK
U2 - 10.1507/endocrj.EJ21-0339
DO - 10.1507/endocrj.EJ21-0339
M3 - Comment/debate
C2 - 34645728
AN - SCOPUS:85124746131
SN - 0918-8959
VL - 69
SP - 319
EP - 326
JO - endocrine journal
JF - endocrine journal
IS - 3
ER -