PMID- 37361044 OWN - NLM STAT- MEDLINE DCOM- 20230630 LR - 20230701 IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 11 DP - 2023 TI - Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population. PG - e15536 LID - 10.7717/peerj.15536 [doi] LID - e15536 AB - OBJECTIVE: The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China. METHODS: A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies. RESULTS: We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all P > 0.05). CONCLUSIONS: The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China. CI - (c)2023 Li et al. FAU - Li, Yan-Peng AU - Li YP AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Adi, Dilare AU - Adi D AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, Ying-Hong AU - Wang YH AD - Center of Health Management, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, Yong-Tao AU - Wang YT AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Li, Xiao-Lei AU - Li XL AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Fu, Zhen-Yan AU - Fu ZY AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Liu, Fen AU - Liu F AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Aizezi, Aibibanmu AU - Aizezi A AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Abuzhalihan, Jialin AU - Abuzhalihan J AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Gai, Mintao AU - Gai M AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ma, Xiang AU - Ma X AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Li, Xiao-Mei AU - Li XM AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Xie, Xiang AU - Xie X AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ma, YiTong AU - Ma Y AD - State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. AD - Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230621 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 RN - 0 (DAB2 protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apoptosis Regulatory Proteins) SB - IM MH - Humans MH - Case-Control Studies MH - *Diabetes Mellitus, Type 2/epidemiology/genetics MH - East Asian People MH - Genetic Predisposition to Disease MH - Polymorphism, Single Nucleotide MH - *Adaptor Proteins, Signal Transducing/genetics MH - *Apoptosis Regulatory Proteins/genetics PMC - PMC10290452 OTO - NOTNLM OT - Diabetes mellitus OT - Gene polymorphism OT - Human Disabled-2 (Dab2) COIS- The authors declare there are no competing interests. EDAT- 2023/06/26 19:07 MHDA- 2023/06/28 06:42 PMCR- 2023/06/21 CRDT- 2023/06/26 12:47 PHST- 2023/01/19 00:00 [received] PHST- 2023/05/19 00:00 [accepted] PHST- 2023/06/28 06:42 [medline] PHST- 2023/06/26 19:07 [pubmed] PHST- 2023/06/26 12:47 [entrez] PHST- 2023/06/21 00:00 [pmc-release] AID - 15536 [pii] AID - 10.7717/peerj.15536 [doi] PST - epublish SO - PeerJ. 2023 Jun 21;11:e15536. doi: 10.7717/peerj.15536. eCollection 2023.