Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Aug;59(4):966-996.
doi: 10.1007/s10528-021-10041-2. Epub 2021 Feb 20.

Association of eNOS and MCP-1 Genetic Variants with Type 2 Diabetes and Diabetic Nephropathy Susceptibility: A Case-Control and Meta-Analysis Study

Priyanka Raina  1 , Ruhi Sikka  1 , Himanshu Gupta  2 , Kawaljit Matharoo  1 , Surinder Kumar Bali  3 , Virinder Singh  4 , Ajs Bhanwer  5
Affiliations
Meta-Analysis

Association of eNOS and MCP-1 Genetic Variants with Type 2 Diabetes and Diabetic Nephropathy Susceptibility: A Case-Control and Meta-Analysis Study

Priyanka Raina et al. Biochem Genet. 2021 Aug.

Abstract

Type 2 diabetes (T2D) and its secondary complications result from the complex interplay of genetic and environmental factors. To understand the role of these factors on disease susceptibility, the present study was conducted to assess the association of eNOS and MCP-1 variants with T2D and diabetic nephropathy (DN) in two ethnically and geographically different cohorts from North India. A total of 1313 subjects from two cohorts were genotyped for eNOS (rs2070744, rs869109213 and rs1799983) and MCP-1 (rs1024611 and rs3917887) variants. Cohort-I (Punjab) comprised 461 T2D cases (204 T2D with DN and 257 T2D without DN) and 315 healthy controls. Cohort-II (Jammu and Kashmir) included 337 T2D (150 T2D with DN and 187 T2D without DN) and 200 controls. Allele, genotype and haplotype frequencies were compared among the studied participants, and phenotype-genotype interactions were determined. Meta-analysis was performed to investigate the association between the selected variants and disease susceptibility. All three eNOS variants were associated with 1.5-4.0-fold risk of DN in both cohorts. MCP-1 rs1024611 conferred twofold risk towards DN progression in cohort-II, while rs3917887 provided twofold risk for both T2D and DN in both cohorts. eNOS and MCP-1 haplotypes conferred risk for T2D and DN susceptibility. Phenotype-genotype interactions showed significant associations between the studied variants and anthropometric and biochemical parameters. In meta-analysis, all eNOS variants conferred risk towards DN progression, whereas no significant association was observed for MCP-1 rs1024611. We show evidences for an association of eNOS and MCP-1 variants with T2D and DN susceptibility.

Keywords: Diabetic nephropathy; Genetic variant; MCP-1; Type 2 diabetes; eNOS.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Figures

Fig. 1
Fig. 1
Genotype–phenotype interaction analysis. Body mass index (BMI), urea, creatinine and random sugar levels were compared between different genotypes of eNOS and MCP-1 gene variants. T bars represent median (in red) and Interquartile Ranges [Data not available for samples: BMI (cohort-I = 15), urea (cohort-I = 181; cohort-II = 1), creatinine (cohort-I = 202; cohort-II = 2) and random sugar (cohort-I = 191; cohort-II = 150)]
Fig. 2
Fig. 2
Forest plot depicting association of eNOS (rs2070744, rs1799983, rs8691092123) and MCP-1 (rs1024611) polymorphisms with DN susceptibility. The area of the square is proportional to the study’s weight. The horizontal line represents a 95% CI. The overall effect is illustrated as diamonds with the lateral points showing CI. Experimental: DN cases; Control: Healthy controls; Events: Allele contrast model (A vs a); W: Weight; CI: Confidence interval. Raina et al_Cohort-I represents Punjab population and Raina et al_Cohort-II represents Jammu and Kashmir population
Fig. 3
Fig. 3
Forest plot depicting association of eNOS (rs2070744, rs1799983, rs8691092123) and MCP-1 (rs1024611) polymorphisms with T2D susceptibility. The area of the square is proportional to the study’s weight. The horizontal line represents a 95% CI. The overall effect is illustrated as diamonds with the lateral points showing CI. Experimental: DN cases; Control: Healthy controls; Events: Allele contrast model (A vs a); W: Weight; CI: Confidence interval. Raina et al_Cohort-I represents Punjab population and Raina et al_Cohort-II represents Jammu and Kashmir population
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahluwalia TS, Ahuja M, Rai TS, Kohli HS, Sud K, Bhansali A, Khullar M. Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. Mol Cell Biochem. 2008;314:9–17. - PubMed
    1. Ahluwalia TS, Khullar M, Ahuja M, Kohli HS, Bhansali A, Mohan V, Venkatesan R, Rai TS, Sud K, Singal PK. Common variants of inflammatory cytokine genes are associated with risk of nephropathy in type 2 diabetes among Asian Indians. PLoS ONE. 2009;4:e5168. doi: 10.1371/journal.pone.0005168. - DOI - PMC - PubMed
    1. American Diabetes Association Standards of Medical Care in Diabetes-2011. Diabetes Care. 2011;34:s11–s61. - PMC - PubMed
    1. Awad AS, You H, Gao T, Cooper TK, Nedospasov SA, Vacher J, Wilkinson PF, Farrell FX, Brian Reeves W. Macrophage-derived tumor necrosis factor-α mediates diabetic renal injury. Kidney Int. 2015;88:722–733. - PMC - PubMed
    1. Bagci B, Bagci G, Candan F, Ozdemir O, Sezgin I. The protective effect of MCP-1 -2518 A>G promoter polymorphism in Turkish chronic renal failure patients requiring long-term hemodialysis. Int Urol Nephrol. 2015;47:551–556. - PubMed

Publication types