scholarly journals The Niemann–Pick C1-like 1 rs2073547 polymorphism is associated with type 2 diabetes mellitus in a Chinese population

2019 ◽  
Vol 47 (9) ◽  
pp. 4260-4271
Author(s):  
Zhenxing Huang ◽  
Ruyin Tan ◽  
Liheng Meng ◽  
Haiyan Yang ◽  
Xinghuan Liang ◽  
...  

Objective To explore the association between Niemann–Pick C1-like 1 gene ( NPC1L1) single nucleotide polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. Methods Using propensity score matching, 490 T2DM patients and 490 matched controls were recruited from 13 communities in Guangxi, China. NPC1L1 rs217386 and rs2073547 genotyping was performed using a MassARRAY system. Results The rs2073547 genotype distribution differed significantly among patient groups. Low-density lipoprotein cholesterol levels were similar among different rs2073547 genotypes and alleles. The rs2073547 AG genotype was significantly more prevalent in patients with T2DM. After adjusting for risk or protective factors for diabetes, AG and GG+AG genotypes of rs2073547 were associated with significantly increased risks of T2DM. Compared with the AA genotype, the AG genotype was associated with a significantly higher risk of T2DM in participants with gamma-glutamyl transpeptidase (GGT) <45 U/L, systolic blood pressure (SBP) ≥140 mmHg, or triglyceride <1.70 mmol/L. In participants with GGT <45 U/L or SBP ≥140 mmHg, the GG+AG genotype was associated with a significantly higher T2DM risk versus the AA genotype. Conclusions The rs2073547 polymorphism of NPC1L1 may be related to T2DM susceptibility in the Chinese population.

2020 ◽  
Author(s):  
Li Jin ◽  
Yan Huang ◽  
Yangyang Li ◽  
Bo Xu ◽  
Cheng Hu ◽  
...  

Abstract Background: CYP2C8 and CYP2C9 are cytochrome P450 epoxygenases that metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs). EETs are important lipid mediators with many beneficial effects in type 2 diabetes mellitus. In this study, we aimed to investigate the association of CYP2C8 and CYP2C9 variants with type 2 diabetes in a Chinese population. Methods: We genotyped 9 tag single nucleotide polymorphisms (SNPs) in CYP2C8 and 10 tag SNPs in CYP2C9 based on HapMap Chinese and Japanese data. Then, we genotyped the SNPs in a Chinese population that included 3410 type 2 diabetes patients and 3401 normal controls. The association between the SNPs and type 2 diabetes was analysed. Results: In the study population, we found that rs1819173 in the CYP2C9 gene region was associated with type 2 diabetes and the A allele was protective against type 2 diabetes (odds ratio: 0.840, 95% confidence interval (CI): 0.780-0.904, P=3.04×10-6). Haplotypes GT and AT (rs2071426-rs6583967) in CYP2C8 were associated with type 2 diabetes (P=0.049 and 0.038, respectively). On the other hand, an interaction effect between rs1819173 in CYP2C9 and rs12766752 in CYP2C8 on type 2 diabetes was found (P=0.003). What’s more, rs1819173 showed significant association with HDL-C (high-density lipoprotein cholesterol).Conclusions: Our results suggested that common SNPs in the CYP2C8 and CYP2C9 regions were associated with T2DM in a Chinese Han population.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zaihan Zhu ◽  
Yanfen Zhang ◽  
Ruocen Bai ◽  
Ru Yang ◽  
Zhongyan Shan ◽  
...  

IntroductionMicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.MethodsFive SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.ResultsIn overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.ConclusionMiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.


2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Nooshin Ghodsian ◽  
Patimah Ismail ◽  
Salma Ahmadloo ◽  
Farzad Heidari ◽  
Polin Haghvirdizadeh ◽  
...  

With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms ofWNK4gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism ofWNK4gene with essential hypertensive patients in Malaysia.WNK4gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation betweenAla589Serpolymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p<0.05). The distribution of allele frequency and genotype ofWNK4geneAla589Serpolymorphism showed significant differences (p<0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. TheWNK4gene variation influences significantly blood pressure increase.Ala589Serprobably has effects on the enzymic activity leading to enhanced predisposition to the disorder.


2018 ◽  
Vol 65 (3) ◽  
Author(s):  
Elena Kazakova ◽  
Meijun Chen ◽  
Esma Jamaspishvili ◽  
Zhang Lin ◽  
Jingling Yu ◽  
...  

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 had relationships with type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined the association of them with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP allele and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had a significant decreased T2DM risk compared to homozygous carriers of TT (p= 0.038, OR 0.44, 95 % CI 0.20-0.96). In the recessive model, the genotype GG carriers had a significant decreased T2DM risk compared to GT+TT (p= 0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of genotype CT and TT had significantly decreased T2DM risk compared with the carriers of genotype CC (CT: CC P=0.038, OR 0.71, 95%CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95%CI 0.13-0.76). In a dominant model, TT+CT: CC (p= 0.013, OR 0.673, 95 % CI 0.49-0.92) and in a recessive model, TT: CT+CC (p= 0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had a significant decreased T2DM risk compared to carriers of C (p= 0.002, OR 0.65, 95 % CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.


2021 ◽  
pp. 5-5
Author(s):  
Karar Musafer ◽  
Fahrul Huyop ◽  
Mufeed Ewadh ◽  
Eko Supriyanto ◽  
Tahreer Al-Thuwaini ◽  
...  

This study was conducted to assess the potential association between leptin (LEP) gene polymorphisms and type 2 diabetes mellitus (T2DM) in Iraqi patients. Genomic DNA was extracted from 120 diabetic subjects and 100 controls. Three specific PCR fragments were designed to flank three highly frequent single nucleotide polymorphism (SNP)s within LEP, rs11761556, rs12706832 and rs2167270. The amplified loci were genotyped by PCR-single-strand conformation polymorphism (SSCP) followed by Sanger sequencing for representative genotypes. Logistic regression analysis was performed to detect the association between the targeted genetic variants and T2DM. PCR-SSCP genotyping showed three banding patterns for all three targeted SNPs. Individuals with the AA genotype in both rs11761556 and rs12706832 SNPs showed significantly higher (P<0.05) body mass index (BMI), waist circumference (WC), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), insulin, low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) values than those with other genotypes. Association analysis revealed that individuals with the A allele exhibited a greater risk of T2DM. Data of the present investigation indicated that both rs11761556 and rs12706832 SNPs exerted a noticeable association with T2DM. The study suggests implementing both rs11761556 and rs12706832 SNPs in the early detection of T2DM.


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