Introduction:
The prevalence of CKD has been increasing, but our understanding of the risk factors and pathogenesis for CKD is limited. Studies have shown important genetic contributions to increasing CKD risk and its progression to ESKD. Page study from the USA identified that NMT2 and APOL1 loci were associated with CKD. There are no studies so far on the Indian population. By identifying the susceptibility loci we can screen the population to identify individuals at risk for CKD and reduce the morbidity and mortality associated with it through early diagnosis and targeted therapy. Also, by identifying the genetic loci, we can understand the underlying pathogenetic mechanism causing CKD and target treatment accordingly.
Methods:
Study population: Pilot study of 90 cases and 90 controls
Cases: Indian population at varying stages of CKD (eGFR <60ml/min/1.73m2)
Control: Healthy controls (normal eGFR according to age).
Exclusion criteria: Patients with a concomitant diagnosis of malignancy, chronic hepatic disease, autoimmune disease.
DNA extraction and genotyping
Genomic DNA was extracted from whole blood by magnetic separation using the QIA Symphony automated DNA isolation system (QIAGEN. Hilden, Germany) following manufacturer’s protocol. Genomic DNA quantification was done on Thermo Scientific™ Multiskan™ Sky Microplate Spectrophotometer (ThermoFisher Scientific, USA). Quality of DNA was checked on agarose gel. Whole genome genotyping was performed using Infinium™ Global Screening Array-24 v3.0 BeadChip (Illumina, Inc, San Diego, California), containing probes that covers ~640k markers. Normalized bead intensity data gained for each sample was run through the GenomeStudio software (Illumina, Inc, San Diego, California), to obtain SNP genotype calls from the fluorescence intensities.
GWAS analysis
The GWAS analysis was performed on a total of 180 samples, including 90 cases and 90 medgenome database controls.Data QC was performed with a genotyping cutoff of 0.95 was applied to filter out low-quality samples.
Results:
The baseline age, gender and co morbidites were matched. The results of genome-wide association studies showed associations of CMTM7 ( Chemokine-like factor gene superfamily), TCF21 (Antisense RNA Inducing Promoter Demethylation), MPP7 (The protein encoded by this gene is a member of the p55 Stardust family of membrane-associated guanylate kinase (MAGUK) proteins, which function in the establishment of epithelial cell polarity), TMEM132C (Transmembrane Protein 132C) is a Protein Coding gene, UQCR11 (Ubiquinol-Cytochrome C Reductase, Complex III Subunit XI) is a Protein Coding gene and CPAM8 (This gene encodes a member of the protease inhibitor I39 -alpha-2-macroglobulin family of proteins) with CKD.
Conclusions:
To our knowledge, this is the first pilot study carried in Indian population linking genetic polymorphisms and CKD.
Acknowledgment: Medgenome pvt ltd for genetic analysis
I have potential conflict of interest to disclose.
This study was funded by Indian society of Nephrology, La renon research grants.
I did not use generative AI and AI-assisted technologies in the writing process.