PMID- 35176079
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 2
DP  - 2022
TI  - Investigation of angiotensin-1 converting enzyme 2 gene (G8790A) polymorphism in 
      patients of type 2 diabetes mellitus with diabetic nephropathy in Pakistani 
      population.
PG  - e0264038
LID - 10.1371/journal.pone.0264038 [doi]
LID - e0264038
AB  - BACKGROUND: Type 2 diabetes mellitus is a multifactorial disease that escalates 
      the risk of other associated complications such as diabetic neuropathy, 
      retinopathy, and nephropathy. Diabetic nephropathy is a microvascular condition 
      that leads to end-stage renal disease (ESRD). There are several genes involved in 
      disease development and it is a challenging task to investigate all of these. 
      Nonetheless, identifying individual gene roles can assist in evaluating the 
      combinatorial effects with other genes. Angiotensin-1 converting enzyme 2 (ACE2), 
      is the key regulator of blood pressure in the Renin-Angiotensin-Aldosterone 
      System that hydrolyzes angiotensin II (vasoconstrictor) into angiotensin 1-7 
      (vasodilator). The association of different variants of the ACE2 with the risk of 
      type 2 diabetes mellitus has been determined in various populations with 
      susceptibility to other complications. This study was aimed to investigate the 
      association of Angiotensin-1 converting enzyme 2 polymorphism, G8790A, with the 
      increased risk of type 2 diabetes mellitus (T2DM) development with the 
      complication of diabetic nephropathy (DN) in the Pakistani population. METHODS: 
      In this case-control study, a total of 100 healthy controls and 100 patients of 
      type 2 diabetes mellitus aged > 40 years, having disease duration >/= 10 years were 
      compared. The G8790A polymorphism in ACE2 was analyzed by allele-specific 
      polymerase chain reaction (AS-PCR). The urinary albumin excretion (UAE), urinary 
      creatinine, and albumin to creatinine ratios (ACR) were determined to assess 
      renal function status. Pearson bivariate correlation coefficients were calculated 
      to investigate the relationship among all the parameters. Crude and adjusted odds 
      ratios were found to determine any risk association between ACE2 G8790A 
      polymorphisms and disease development. The p-values < 0.05 were considered 
      significant. RESULTS: A homogeneity was obtained regarding the distribution of 
      data by sex, BMI, diastolic blood pressure, pulse rate and urinary creatinine 
      levels between case and control groups. The ACR showed a significant correlation 
      with UAE (r = 0.524, p = 0.001), urinary creatinine (r = -0.375, p = 0.001) and 
      random blood sugar levels (r = 0.323, p = 0.005) with the complication of 
      diabetic nephropathy in T2DM patient. Females with the AA genotype had a 10-fold 
      increased risk for the development of type 2 Diabetes (OR = 9.5 [95% CI = 
      2.00-21.63] p<0.002). Males having A allele showed a significant association for 
      susceptibility of type 2 Diabetes (OR = 3.807 [95% CI = 1.657-8.747] p<0.002). 
      However, none of the genotypes or alleles revealed an association for diabetic 
      nephropathy in male and female patients. Urinary ACR was also found to be 
      positively correlated with UAE (r = 0.642 p = 0.001 & 0.524, p = 0.001) and 
      random blood sugar levels (r = 0.302, p = 0.002 & r = 0.323, p = 0.005) in T2DM 
      and T2DM+DN groups, respectively. CONCLUSION: The study finding indicated that 
      female AG/AA genotype and male A genotype of G8790A polymorphism in the ACE2 gene 
      were associated with type 2 diabetes mellitus as a genetic risk factor but are 
      not associated with diabetic nephropathy in the Pakistani population.
FAU - Younas, Hooria
AU  - Younas H
AUID- ORCID: 0000-0002-1533-7680
AD  - Department of Biochemistry, Kinnaird College for Women, Lahore, Punjab, Pakistan.
FAU - Ijaz, Tahira
AU  - Ijaz T
AD  - Department of Biochemistry, Kinnaird College for Women, Lahore, Punjab, Pakistan.
FAU - Choudhry, Nakhshab
AU  - Choudhry N
AD  - Department of Biochemistry, King Edward Medical University, Lahore, Punjab, 
      Pakistan.
LA  - eng
PT  - Journal Article
DEP - 20220217
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Adult
MH  - Angiotensin-Converting Enzyme 2/*genetics
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/complications/*genetics/pathology
MH  - Diabetic Nephropathies/epidemiology/etiology/metabolism/*pathology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pakistan/epidemiology
MH  - *Polymorphism, Genetic
PMC - PMC8853542
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/02/18 06:00
MHDA- 2022/03/01 06:00
PMCR- 2022/02/17
CRDT- 2022/02/17 17:14
PHST- 2021/11/03 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/02/17 17:14 [entrez]
PHST- 2022/02/18 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2022/02/17 00:00 [pmc-release]
AID - PONE-D-21-35011 [pii]
AID - 10.1371/journal.pone.0264038 [doi]
PST - epublish
SO  - PLoS One. 2022 Feb 17;17(2):e0264038. doi: 10.1371/journal.pone.0264038. 
      eCollection 2022.