Browsing by Author "Park JH"

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    Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study
    (BMC, 2020-08-05) Bae JB; Lipnicki DM; Han JW; Sachdev PS; Kim TH; Kwak KP; Kim BJ; Kim SG; Kim JL; Moon SW; Park JH; Ryu S-H; Youn JC; Lee DY; Lee DW; Lee SB; Lee JJ; Jhoo JH; Llibre-Rodriguez JJ; Llibre-Guerra JJ; Valhuerdi-Cepero AJ; Ritchie K; Ancelin M-L; Carriere I; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis E; Meguro K; Kasai M; Nakamura K; Riedel-Heller S; Roehr S; Pabst A; van Boxtel M; Köhler S; Ding D; Zhao Q; Liang X; Scazufca M; Lobo A; De-la-Cámara C; Lobo E; Kim KW; for Cohort Studies of Memory in an International Consortium (COSMIC)
    Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.
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    EP400NL is involved in PD-L1 gene activation by forming a transcriptional coactivator complex
    (Elsevier B V, 2023-03) Li Z; Kim H; Kim J; Park JH
    EP400 is an ATP-dependent chromatin remodelling enzyme that regulates DNA double-strand break repair and transcription, including cMyc-dependent gene expression. We previously showed that the N-terminal domain of EP400 increases the efficacy of chemotherapeutic drugs against cancer cells. As the EP400 N-terminal-Like (EP400NL) gene resides next to the EP400 gene locus, this prompted us to investigate whether EP400NL plays a similar role in transcriptional regulation to the full-length EP400 protein. We found that EP400NL forms a human NuA4-like chromatin remodelling complex that lacks both the TIP60 histone acetyltransferase and EP400 ATPase. However, this EP400NL complex displays H2A.Z deposition activity on a chromatin template comparable to the human NuA4 complex, suggesting another associated ATPase such as BRG1 or RuvBL1/RuvBL2 catalyses the reaction. We demonstrated that the transcriptional coactivator function of EP400NL is required for serum and IFNγ-induced PD-L1 gene activation. Furthermore, transcriptome analysis indicates that EP400NL contributes to cMyc-responsive mitochondrial biogenesis. Taken together, our studies show that EP400NL plays a role as a transcription coactivator of PD-L1 gene regulation and provides a potential target to modulate cMyc functions in cancer therapy.
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    Parity and the risk of incident dementia: a COSMIC study
    (Cambridge University Press, 2020-10-20) Bae JB; Lipnicki DM; Han JW; Sachdev PS; Kim TH; Kwak KP; Kim BJ; Kim SG; Kim JL; Moon SW; Park JH; Ryu S-H; Youn JC; Lee DY; Lee DW; Lee SB; Lee JJ; Jhoo JH; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis E; Riedel-Heller S; Roehr S; Pabst A; Ding D; Zhao Q; Liang X; Lobo A; De-la-Cámara C; Lobo E; Kim KW; for Cohort Studies of Memory in an International Consortium (COSMIC)
    Aims To investigate the association between parity and the risk of incident dementia in women. Methods We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). Results Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity. Conclusions Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.