PMID- 35570489
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20221207
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 88
IP  - 1
DP  - 2022
TI  - Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with 
      Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.
PG  - 241-249
LID - 10.3233/JAD-220036 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to increase the risks 
      of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription 
      factor for beta cell development and function, has recently been implicated in 
      pathways intersecting Alzheimer's disease and T2DM. OBJECTIVE: In this report, we 
      evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk 
      factor for East Asians which contributes to earlier diabetes onset, and cognitive 
      function of Chinese T2DM patients. METHODS: 590 Chinese patients aged 45-86 from 
      the SMART2D study were genotyped for PAX4 R192H variation using Illumina 
      OmniExpress-24 Array. The Repeatable Battery for the Assessment of 
      Neuropsychological Status (RBANS) which had been validated in the Singapore 
      population was administered to assess five cognitive domains: immediate memory, 
      visuospatial/constructional, language, attention, and delayed memory. Multiple 
      linear regression was used to assess the association of the R192H risk allele and 
      cognitive domains. RESULTS: Patients with two PAX4 R192H risk alleles showed 
      significantly lower attention index score (beta= -8.46, 95% CI [-13.71, -3.21], 
      p = 0.002) than patients with wild-type alleles after adjusting for age, gender, 
      diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, 
      systolic blood pressure, metformin usage, smoking history, education level, 
      Geriatric Depression Scale score, and presence of APOEvarepsilon4 allele. CONCLUSION: 
      Ethnic-specific R192H variation in PAX4 is associated with attention-specific 
      cognitive impairment in Chinese with T2DM. Pending further validation studies, 
      determining PAX4 R192H genotype may be helpful for early risk assessment of 
      early-onset T2DM and cognitive impairment to improve diabetes care.
FAU - Ang, Su Fen
AU  - Ang SF
AD  - Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
FAU - Low, Serena
AU  - Low S
AD  - Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
FAU - Ng, Tze Pin
AU  - Ng TP
AD  - Department of Psychological Medicine, Gerontology Research Programme, Yong Loo 
      Lin School of Medicine, National University of Singapore, Singapore.
FAU - Tan, Clara S H
AU  - Tan CSH
AD  - Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
FAU - Ang, Keven
AU  - Ang K
AD  - Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
FAU - Lim, Ziliang
AU  - Lim Z
AD  - National Healthcare Group Polyclinics (NHGP), Singapore.
FAU - Tang, Wern Ee
AU  - Tang WE
AD  - National Healthcare Group Polyclinics (NHGP), Singapore.
FAU - Subramaniam, Tavintharan
AU  - Subramaniam T
AD  - Diabetes Centre, Admiralty Medical Centre (AdMC) c/o Khoo Teck Puat Hospital, 
      Singapore.
FAU - Sum, Chee Fang
AU  - Sum CF
AD  - Diabetes Centre, Admiralty Medical Centre (AdMC) c/o Khoo Teck Puat Hospital, 
      Singapore.
FAU - Lim, Su Chi
AU  - Lim SC
AD  - Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
AD  - Diabetes Centre, Admiralty Medical Centre (AdMC) c/o Khoo Teck Puat Hospital, 
      Singapore.
AD  - Saw Swee Hock School of Public Health, National University of Singapore (NUS), 
      Singapore.
AD  - Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), 
      Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Homeodomain Proteins)
RN  - 0 (PAX4 protein, human)
RN  - 0 (Paired Box Transcription Factors)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People/genetics
MH  - Attention
MH  - China
MH  - *Cognitive Dysfunction
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Homeodomain Proteins/genetics
MH  - Humans
MH  - Language
MH  - Middle Aged
MH  - Paired Box Transcription Factors/genetics/metabolism
MH  - Risk Factors
OTO - NOTNLM
OT  - Cognitive impairment
OT  - PAX4
OT  - ethnic-specific
OT  - type 2 diabetes
EDAT- 2022/05/17 06:00
MHDA- 2022/07/08 06:00
CRDT- 2022/05/16 02:43
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/05/16 02:43 [entrez]
AID - JAD220036 [pii]
AID - 10.3233/JAD-220036 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2022;88(1):241-249. doi: 10.3233/JAD-220036.