PMID- 32512158
OWN - NLM
STAT- MEDLINE
DCOM- 20200805
LR  - 20221207
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 754
DP  - 2020 Sep 5
TI  - Association analysis of polymorphisms in LEP (rs7799039 and rs2167270) and LEPR 
      (rs1137101) gene towards the development of type 2 diabetes in North Indian 
      Punjabi population.
PG  - 144846
LID - S0378-1119(20)30515-1 [pii]
LID - 10.1016/j.gene.2020.144846 [doi]
AB  - OBJECTIVES: Obesity is a major risk factor in aetiology of type 2 diabetes 
      mellitus (T2DM). Leptin (LEP) is an anti-obesity hormone which regulates food 
      intake, energy expenditure and glucose metabolism. The genetic variants in leptin 
      and leptin receptor gene (LEPR) may play major role in the pathogenesis of T2DM 
      and obesity. The current study aimed to investigate the association of 
      polymorphisms in LEP (rs7799039, -2548G/A and rs2167270, 19G/A) and LEPR 
      (rs1137101, 668A/G) gene with type 2 diabetes in North Indian Punjabi population. 
      METHODS: A total of 817 subjects were included for the present case-control 
      study, consisting of 417 T2DM patients and 400 healthy controls. The 
      anthropometric, physiometric and biochemical measurements were taken from all the 
      subjects. The genotyping of LEP and LEPR gene variants were carried out by 
      polymerase chain reaction based restriction fragment length polymorphism method 
      (PCR-RFLP), followed by genotyping of 10% of the samples for each polymorphism by 
      Sanger sequencing method for quality control measurement. RESULTS: The risk 
      genotype frequencies were found to be significantly higher in T2DM cases than 
      control subjects (rs7799039, p = 0.001; rs2167270, p = 0.019 and rs1137101, 
      p = 0.003). Under recessive genetic model LEPrs7799039 and LEPRrs1137101 
      polymorphism conferred 3.4 and 2.1 fold risk towards the development of T2DM 
      after adjustment of various covariates (OR = 3.44, 95%CI: 1.768-6.681, p = 0.001 
      and OR: 2.12, 95%CI: 1.256-3.569, p = 0.005, respectively). In the stratified 
      analysis of LEP variant rs7799039 by age, gender, BMI and alcohol use, a 
      significantly increased risk of T2DM was found in female, BMI >/= 23 and never 
      drinking subgroups. However, in the LEPR variant rs1137101, significantly 
      increased risk of T2DM was observed in age <50, male, BMI >/= 23 and never drinking 
      subgroup. The A-G haplotype combination of rs7799039A and rs2167270G conferred 
      significant 2 fold risk towards T2DM (OR = 2.35, 95%CI: 1.34-4.12, p = 0.002). In 
      control group, the genetic variants rs7799039 and rs1137101 were significantly 
      associated with levels of random blood sugar and low density lipoprotein 
      cholesterol levels. CONCLUSION: The present study revealed the association of LEP 
      rs7799039 and LEPR rs1137101 with type 2 diabetes mellitus, which suggest its 
      predominant role in the estimation of type 2 diabetes mellitus in North Indian 
      Punjabi population.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Bains, Veena
AU  - Bains V
AD  - Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar 143 005, 
      Punjab, India.
FAU - Kaur, Harjit
AU  - Kaur H
AD  - Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar 143 005, 
      Punjab, India.
FAU - Badaruddoza, Badaruddoza
AU  - Badaruddoza B
AD  - Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar 143 005, 
      Punjab, India. Electronic address: doza13@yahoo.co.in.
LA  - eng
PT  - Journal Article
DEP - 20200605
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Leptin)
RN  - 0 (Receptors, Leptin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asian People/*genetics
MH  - Biomarkers/analysis
MH  - Blood Glucose/analysis
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*epidemiology/genetics/pathology
MH  - Female
MH  - Follow-Up Studies
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - India/epidemiology
MH  - Leptin/*genetics
MH  - Male
MH  - Middle Aged
MH  - Obesity/*physiopathology
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Receptors, Leptin/*genetics
OTO - NOTNLM
OT  - BMI
OT  - Haplotype
OT  - LD
OT  - LEP
OT  - LEPR
OT  - Polymorphism
OT  - T2DM
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/06/09 06:00
MHDA- 2020/08/06 06:00
CRDT- 2020/06/09 06:00
PHST- 2019/08/28 00:00 [received]
PHST- 2020/05/29 00:00 [revised]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2020/08/06 06:00 [medline]
PHST- 2020/06/09 06:00 [entrez]
AID - S0378-1119(20)30515-1 [pii]
AID - 10.1016/j.gene.2020.144846 [doi]
PST - ppublish
SO  - Gene. 2020 Sep 5;754:144846. doi: 10.1016/j.gene.2020.144846. Epub 2020 Jun 5.