PMID- 36271348
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221028
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 23
IP  - 1
DP  - 2022 Oct 21
TI  - Association of mTORC1‑dependent circulating protein levels with cataract 
      formation: a mendelian randomization study.
PG  - 719
LID - 10.1186/s12864-022-08925-7 [doi]
LID - 719
AB  - BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a 
      critical regulating role in the occurrence and development of cataract. However, 
      the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), 
      eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation 
      factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic 
      initiation factor 4A (EIF-4A), in regulating cataract development is still 
      unknown. Herein, we conducted a mendelian randomization (MR) study to understand 
      the function of mTORC1 signaling in the process of cataract development. RESULTS: 
      The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, 
      weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. 
      RAPS). The single-nucleotide polymorphisms (SNPs), P<5 x 10(- 6) and r(2)<0.05, 
      were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and 
      EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR 
      study. The study revealed causal association between circulating EIF4EBP (OR 
      1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% 
      confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW 
      estimate. Whereas after correcting outliers, MR robust adjusted profile score 
      (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 
      95%CI:1.05-1.11, P = 0.007). The observation strengthened the confidence in the 
      true causal associations. However, no association was found for circulating 
      EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 
      95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% 
      confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No 
      evidence of heterogeneity and unbalanced horizontal pleiotropy was detected. 
      CONCLUSION: The MR study suggests that EIF4EBP is a high-risk factor for cataract 
      development. There may be a potential causal association between the 
      mTORC1/EIF4EBP axis and cataract. This research highlights the potential 
      mechanism for cataract development and a genetic target to prevent as well as 
      treat cataracts.
CI  - (c) 2022. The Author(s).
FAU - Cai, Yingjun
AU  - Cai Y
AD  - Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Central 
      South University, 410008, Changsha, Hunan, China.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 
      Central South University, 410008, Changsha, Hunan, China.
FAU - Liu, Kangcheng
AU  - Liu K
AD  - Jiangxi Clinical Research center for Ophthalmic Disease, Jiangxi Research 
      Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of 
      Nanchang University, Nanchang, China.
FAU - Wu, Pengfei
AU  - Wu P
AD  - Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South 
      University, Changsha, China.
FAU - Yuan, Ruolan
AU  - Yuan R
AD  - Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Central 
      South University, 410008, Changsha, Hunan, China.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 
      Central South University, 410008, Changsha, Hunan, China.
FAU - He, Fei
AU  - He F
AD  - The First Affiliated Hospital of Nanchang University, Nanchang, China.
FAU - Zou, Jing
AU  - Zou J
AD  - Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Central 
      South University, 410008, Changsha, Hunan, China. jzou30@csu.edu.cn.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 
      Central South University, 410008, Changsha, Hunan, China. jzou30@csu.edu.cn.
LA  - eng
GR  - NO. 2022JJ40855/Jing Zou/
GR  - NO. 2022JJ40855/Jing Zou/
GR  - NO. 2022JJ40855/Jing Zou/
GR  - NO. 2022JJ40855/Jing Zou/
GR  - NO. 2022JJ40855/Jing Zou/
GR  - NO. 2022JJ40855/Jing Zou/
PT  - Journal Article
DEP - 20221021
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Cataract/genetics
MH  - Eukaryotic Initiation Factor-4A
MH  - Eukaryotic Initiation Factor-4E/genetics
MH  - *Eukaryotic Initiation Factor-4G
MH  - Genome-Wide Association Study
MH  - Mechanistic Target of Rapamycin Complex 1/genetics
MH  - Mendelian Randomization Analysis
MH  - Polymorphism, Single Nucleotide
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases/genetics
PMC - PMC9587558
OTO - NOTNLM
OT  - Cataract
OT  - Circulating
OT  - EIF4EBP
OT  - Mendelian randomization
OT  - mTOR
COIS- No potential conflicts of interest were disclosed by the authors.
EDAT- 2022/10/23 06:00
MHDA- 2022/10/26 06:00
PMCR- 2022/10/21
CRDT- 2022/10/22 00:22
PHST- 2022/05/30 00:00 [received]
PHST- 2022/09/28 00:00 [accepted]
PHST- 2022/10/22 00:22 [entrez]
PHST- 2022/10/23 06:00 [pubmed]
PHST- 2022/10/26 06:00 [medline]
PHST- 2022/10/21 00:00 [pmc-release]
AID - 10.1186/s12864-022-08925-7 [pii]
AID - 8925 [pii]
AID - 10.1186/s12864-022-08925-7 [doi]
PST - epublish
SO  - BMC Genomics. 2022 Oct 21;23(1):719. doi: 10.1186/s12864-022-08925-7.