PMID- 34258292
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20220117
IS  - 2314-6753 (Electronic)
IS  - 2314-6745 (Print)
VI  - 2021
DP  - 2021
TI  - Association of HLA-B Gene Polymorphisms with Type 2 Diabetes in Pashtun Ethnic 
      Population of Khyber Pakhtunkhwa, Pakistan.
PG  - 6669731
LID - 10.1155/2021/6669731 [doi]
LID - 6669731
AB  - Human leukocyte antigen (HLA) system is the most polymorphic and gene dense 
      region of human DNA that has shown many disease associations. It has been further 
      divided into HLA classes I, II, and III. Polymorphism in HLA class II genes has 
      been reported to play an important role in the pathogenesis of type 1 diabetes 
      (T1D). It also showed association with T2D in different ethnic populations. 
      However, a little is known about the relationship of HLA class I gene 
      polymorphism and T2D. This study has evaluated the association of HLA-B (class I 
      gene) variants with T2D in Pashtun ethnic population of Khyber Pakhtunkhwa. In 
      the first phase of the study, whole exome sequencing (WES) of 2 pooled DNA 
      samples was carried out, and DNA pools used were constructed from 100 diabetic 
      cases and 100 control subjects. WES results identified a total of n = 17 SNPs in 
      HLA-B gene. In the next phase, first 5 out of n = 17 reported SNPs were genotyped 
      using MassARRAY(R) system in order to validate WES results and to confirm 
      association of selected SNPs with T2D. Minor allele frequencies (MAFs) and 
      selected SNPsxT2D association were determined using chi-square test and logistic 
      regression analysis. The frequency of minor C allele was significantly higher in 
      the T2D group as compared to control group (45.0% vs. 13.0%) (p = 0.006) for 
      rs2308655 in HLA-B gene. No significant difference in MAF distribution between 
      cases and controls was observed for rs1051488, rs1131500, rs1050341, and 
      rs1131285 (p > 0.05). Binary logistic regression analyses showed significant 
      results for SNP rs2308655 (OR = 2.233, CI (95%) = 1.223-4.077, and p = 0.009), 
      while no considerable association was observed for the other 4 SNPs. However, 
      when adjusted for these variants, the association of rs2308655 further 
      strengthened significantly (adjusted OR = 7.485, CI (95%) = 2.353-23.812, and p = 
      0.001), except for rs1131500, which has no additive effect. In conclusion, the 
      finding of this study suggests rs2308655 variant in HLA-B gene as risk variant 
      for T2D susceptibility in Pashtun population.
CI  - Copyright (c) 2021 Asif Jan et al.
FAU - Jan, Asif
AU  - Jan A
AUID- ORCID: 0000-0003-3880-5579
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
FAU - Saeed, Muhammad
AU  - Saeed M
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
FAU - Afridi, Muhammad Hussain
AU  - Afridi MH
AD  - Diabetes and Endocrinology Unit, Hayatabad Medical Complex Peshawar, Pakistan.
FAU - Khuda, Fazli
AU  - Khuda F
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
FAU - Shabbir, Muhammad
AU  - Shabbir M
AD  - Internal Medicine, College of Medicine, Shaqra University, Saudi Arabia.
FAU - Khan, Hamayun
AU  - Khan H
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
FAU - Ali, Sajid
AU  - Ali S
AD  - Department of Biotechnology, Abdul Wali Khan University, Mardan, Pakistan.
FAU - Hassan, Muhammad
AU  - Hassan M
AD  - Pakistan Air Force Hospital, Fort Munro, Pakistan.
FAU - Samiullah
AU  - Samiullah
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
FAU - Akbar, Rani
AU  - Akbar R
AD  - Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.
FAU - Zakiullah
AU  - Zakiullah
AUID- ORCID: 0000-0001-7932-9498
AD  - Department of Pharmacy, University of Peshawar, Pakistan.
LA  - eng
PT  - Journal Article
DEP - 20210616
PL  - England
TA  - J Diabetes Res
JT  - Journal of diabetes research
JID - 101605237
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Aged
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Ethnicity/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA-B Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pakistan
MH  - Polymorphism, Single Nucleotide
PMC - PMC8254654
COIS- Authors declare no competing interests.
EDAT- 2021/07/15 06:00
MHDA- 2022/01/18 06:00
PMCR- 2021/06/16
CRDT- 2021/07/14 07:09
PHST- 2021/01/03 00:00 [received]
PHST- 2021/04/20 00:00 [revised]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/07/14 07:09 [entrez]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/06/16 00:00 [pmc-release]
AID - 10.1155/2021/6669731 [doi]
PST - epublish
SO  - J Diabetes Res. 2021 Jun 16;2021:6669731. doi: 10.1155/2021/6669731. eCollection 
      2021.