PMID- 32708841
OWN - NLM
STAT- MEDLINE
DCOM- 20210317
LR  - 20210317
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 11
IP  - 7
DP  - 2020 Jul 17
TI  - TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin 
      Resistance in Obese Female Subjects.
LID - 10.3390/genes11070814 [doi]
LID - 814
AB  - BACKGROUND: Activation of Toll-like-receptor 4 (TLR4) causes chronic inflammation 
      that can result in obesity and metabolic syndrome (MeS). AIM: This study aimed to 
      investigate the role of TLR4 polymorphisms of TLR4D299G/T399I, and its impact on 
      protein expression of TLR4 in obese female subjects. METHODOLOGY: A prospective 
      cross-sectional association study was performed on Arab female subjects from 
      Qatar University. The subjects were categorized according to BMI classifications 
      into two groups: "obese; n = 69" and "non-obese; n = 136". Anthropometric 
      measurements, weight (kg), height (m) and waist circumference (WC) were 
      evaluated, and the body mass index (BMI) was calculated. Fasting blood samples 
      were collected, and assessment of glucose, lipid profile, C-reactive protein 
      (CRP), leptin, IL-6 and insulin was performed. Insulin resistance was computed 
      using HOMA-IR. Genotyping of the TLR4 polymorphisms of TLR4D299G (rs4986790) and 
      TLR4T399I (rs4986791) was performed by the 5' nuclease assay by TaqMan MGB probe. 
      Flow cytometry was used to evaluate the monocyte cell surface expression of TLR4. 
      RESULTS: The frequency distribution of the genotype revealed that homozygous AA 
      is the most frequent among obese subjects (86.4%) for (TLR4D299G, A > G) and the 
      homozygous CC genotype is the most frequent (92.4%) for (TLR4T399I, C > T). 
      Haplotype analysis of TLR4 D299G/T399I showed that GT carriers had a significant 
      association with increased probability of insulin resistance (odds ratio = 4.73; 
      95% CI 1.19-18.90; p-value = 0.016). The monocyte cell surface of TLR4 was 
      significantly higher by 1.3 folds in obese compared to non-obese subjects. 
      CONCLUSIONS: TLR4 D299G/T399I haplotype polymorphism is associated with an 
      increased risk of insulin resistance with the upregulation of TLR4 protein 
      expression in obese subjects.
FAU - Sharif, Elham
AU  - Sharif E
AD  - Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar 
      University, Doha 2713, Qatar.
FAU - Al-Wakeel, Mariam
AU  - Al-Wakeel M
AUID- ORCID: 0000-0002-9030-1696
AD  - Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar 
      University, Doha 2713, Qatar.
FAU - Mohamed, Afnan
AU  - Mohamed A
AD  - Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar 
      University, Doha 2713, Qatar.
FAU - Kerkadi, Abdelhamid
AU  - Kerkadi A
AD  - Human Nutrition Department, College of Health Sciences, QU Health, Qatar 
      University, Doha 2713, Qatar.
FAU - Rizk, Nasser
AU  - Rizk N
AUID- ORCID: 0000-0002-6288-3609
AD  - Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar 
      University, Doha 2713, Qatar.
AD  - Biomedical Research Center, Qatar University, Doha 2713, Qatar.
AD  - Physiology Department, Mansoura Faculty of Medicine, Mansoura 35516, Egypt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200717
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adult
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Obesity/*genetics/metabolism
MH  - *Polymorphism, Single Nucleotide
MH  - Toll-Like Receptor 4/*genetics
PMC - PMC7397302
OTO - NOTNLM
OT  - TLR4 polymorphism
OT  - haplotype
OT  - insulin resistance and obesity
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2020/07/28 06:00
MHDA- 2021/03/18 06:00
PMCR- 2020/07/01
CRDT- 2020/07/26 06:00
PHST- 2020/06/17 00:00 [received]
PHST- 2020/07/01 00:00 [revised]
PHST- 2020/07/06 00:00 [accepted]
PHST- 2020/07/26 06:00 [entrez]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2021/03/18 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - genes11070814 [pii]
AID - genes-11-00814 [pii]
AID - 10.3390/genes11070814 [doi]
PST - epublish
SO  - Genes (Basel). 2020 Jul 17;11(7):814. doi: 10.3390/genes11070814.