{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:36:09Z","timestamp":1770140169490,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p &lt; 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22\u201312.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31\u20134.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p &lt; 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p &lt; 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM.<\/jats:p>","DOI":"10.3390\/cimb47070530","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T11:26:37Z","timestamp":1752233197000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Nrf2 Single Nucleotide Polymorphism rs35652124 and FABP4 Levels with Peripheral Artery Disease Among Type 2 Diabetes Mellitus Pakistani Population"],"prefix":"10.3390","volume":"47","author":[{"given":"Iqra","family":"Ayaz","sequence":"first","affiliation":[{"name":"Department of Pathology, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nakhshab","family":"Choudhry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna","family":"Ihsan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0494-4626","authenticated-orcid":false,"given":"Tehreem","family":"Zubair","sequence":"additional","affiliation":[{"name":"Department of Medicine, Al-Aleem Medical College, Lahore 54600, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4379-0578","authenticated-orcid":false,"given":"Aamir Jamal","family":"Gondal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-6093","authenticated-orcid":false,"given":"Nighat","family":"Yasmin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41586-020-2263-3","article-title":"Identification of type 2 diabetes loci in 433,540 East Asian individuals","volume":"582","author":"Spracklen","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.cmet.2014.12.020","article-title":"Rare and common genetic events in type 2 diabetes: What should biologists know?","volume":"21","author":"Bonnefond","year":"2015","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s40001-024-01739-1","article-title":"Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: A comprehensive review","volume":"29","author":"Guan","year":"2024","journal-title":"Eur. 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