Association analysis of HHEX gene variant with type 2 diabetes risk
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ORIGINAL ARTICLE
Association analysis of HHEX gene variant with type 2 diabetes risk Pantea Banihashemi 1 & Hamid Reza Aghaei Meybodi 2 Mandana Hasanzad 1
&
Mahdi Afshari 3
&
Negar Sarhangi 2
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Received: 27 March 2020 / Accepted: 1 September 2020 # Research Society for Study of Diabetes in India 2020
Abstract Background Type 2 diabetes mellitus (T2DM) is a common, chronic, and complex disorder that is influenced by interactions between genetic and environmental factors. The hematopoietically expressed homeobox (HHEX) gene, which affects insulin sensitivity and secretion, is a candidate gene for the pathogenesis of T2DM. Objective The purpose of this study was to investigate the effect of the HHEX genetic variant, rs1111875, on the T2DM risk in a group of Iranian patients for the first time. Methods A total of 108 T2DM patients and 100 normal subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results There was significant difference in genotypes and alleles frequency of rs1111875 between both case and control groups (p < 0.001). The frequency of the G allele was significantly higher in cases (87.5%) compared with controls (27%) (OR = 18.92, CI = 11.06–32.69, p < 0.001). Conclusion Our findings suggest that the rs1111875 variant of the HHEX gene could be considered a strong risk factor for T2DM development. Keywords HHEX . rs1111875 . T2DM . Genetic variant
Introduction Type 2 diabetes mellitus (T2DM) is a complex, metabolic, multifactorial disorder resulting from interactions between genetic and environmental factors [1–3]. T2DM is caused by insulin resistance in muscles and fat cells, decreased insulin secretion, and increased hepatic glucose production [4, 5]. Patients with T2DM may suffer from macrovascular and
* Hamid Reza Aghaei Meybodi [email protected] * Mandana Hasanzad [email protected] 1
Medical Genomics Research Center, Tehran Medical Sciences, Islamic Azad University, Khaghani Avenue, Shariati St, Tehran 193951459, Iran
2
Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, No.10- Jalal -e-Ale-Ahmad Street, Chamran Highway, Tehran 1411713119, Iran
3
Department of Community Medicine, Zabol University of Medical Sciences, Zabol, Iran
microvascular complications such as cardiovascular disease, neuropathy, nephropathy, and retinopathy, which are associated with a marked morbidity and mortality, decrease the quality of life, and have negative economic effects on countries [6, 7]. Genome-wide association studies (GWAS) have shown a large number of genes associated with T2DM, including TCF7L2, SLC30A8, IGF2BP2, CDKN2A, CDKN2B, CDKAL1, HHEX, EXT2, LOC387761, FTO, PPARG, KCNQ1, and JAZF1 [2, 8]. Identifying more genetic variants can help to predict and prevent T2DM [9]. In 2007, hematopoietically expressed homeobox (HHEX) was introduced as a new locus for T2DM [8]. It encodes a transcription factor involved in Wnt signaling and is required for pancre
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