TP53 codon 72 polymorphism and type 2 diabetes: a case–control study in South Indian population

Molecular Biology Reports - TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor...     

Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer susceptibility: evidence from 27 case–control studies

Genome-wide association studies have identified two SNPs (rs402710 and rs401681) of CLPTM1L at chromosome 5p15.33 as a new lung cancer (LC) susceptibility locus in populations of European descent. Since then, the relationship between these SNPs and LC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 27 studies involving a total of 60,828 cases and 109,135 controls for the two polymorphisms to evaluate its effect on genetic susceptibility for LC. An overall random-effects per-allele odds ratio of 1.14 (95 % CI 1.11–1.16, P < 10^?5) and 1.15 (95 % CI 1.12–1.19, P < 10^?5) was found for the rs401681 and rs402710 polymorphism, respectively. Significant results were also observed for under dominant and recessive genetic models. After stratified by ethnicity, significant associations were found among Caucasians and East Asians. In the subgroup analysis by sample size, significantly increased risks were found for these polymorphisms in all genetic models. In addition, we find both rs402710 and rs401681 conferred significantly greater risks for adenocarcinoma and squamous cell carcinoma when stratified by histological type of tumors. Furthermore, associations of these polymorphisms with LC risk were observed among current smokers and former smokers, as well as never smokers. Our findings demonstrated that rs402710 and rs401681 are risk-conferring factors for the development of lung cancer.     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

Impact of variants on type-2 diabetes risk genes identified through genomewide association studies in polycystic ovary syndrome: a case–control study

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females, and is associated with altered metabolic processes in particular insulin resistance and diabetes mellitus. PCOS shares with type-2 diabetes (T2D) a number of features, including beta cell dysfunction, impaired glucose tolerance and dyslipidaemia. Recently, genomewide association studies (GWAS) have reported a number of genes with reproducible associations and susceptibilities to T2D. To address this, we examined the association between the T2D GWAS candidate genes (CDKAL1, CDKN2B, COL8A1, HHEX, IGF2BP2, KCNJ1, KCNQ1 and SLC30A8) and PCOS in Saudi women. A case–control study, includes 162 cases and 162 controls was enrolled. Genotyping was carried out by the allelic discrimination method. Our results showed that the variants including rs792837 of COL8A1, rs61873498 of KCNQ1 and rs13266634 of SLC30A8 genes to be significantly more frequent in PCOS patients than in controls. Our results suggest that COL8A1, KCNQ1 and SLC30A8, which are previously identified through GWAS as T2D-associated genes, are associated with PCOS.     

Association between self-care management practices and glycemic control of patients with type 2 diabetes mellitus in Saud Arabia: A cross –sectional study

ObjectiveIn this cross-sectional study, we aimed to determine the association of self-care management practices and glycemic control of type 2 diabetes mellitus in Saudi Arabia.MethodsA total of 352 type 2 diabetes mellitus (T2DM) patients from two public tertiary hospitals in Saudi Arabia participated in this study. All T2DM patients were recruited and interviewed by a researcher between January to April 2018 from the outpatient diabetes clinics. All respondents answered a four-part questionnaire which includes demographics data, Diabetes Self-Management Questionnaire (DSMQ). Linear Regression was performed to assess the significance of predictors and compute the coefficient of determination.ResultsThe mean age of the participants was 51.89 ± 10.94. Of the 352 participants, 52% were obese (BMI: ≥30 kgm²) and 77% of the participants had glycated haemoglobin (HbA1c) over 7%. The analysis showed that subscale of Glucose management was the strongest predictor of Hba1c levels of participants’ followed by physical activity. Gender and marital status emerged as significant predictors for their self-care management practices. Female patients had more self-care management practices than male patients (B 0.20; 95CI 0.10– 0.96 (p = 0.015).ConclusionThis study provides an evidence on the self-care management of T2DM patients in Saudi Arabia. The high self-care management found in the study highlights that the patients are aware of the severity of and possible complications associated with T2DM.     

ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes

Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin–angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene–gene interaction between acetyl-coenzymeA carboxylase beta (ACACβ) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier. The present study was designed with the aim to examine the association of an ACACβ (rs2268388) and AGTR1 (rs5186) gene polymorphism with the risk of DN in Asian Indians. 1,158 patients with T2DM belonging to two independently ascertained North Indian and one South Indian cohorts were genotyped for ACACβ (rs2268388) and AGTR1 (rs5186) polymorphism using real time PCR-based Taq-man assay and PCR–RFLP assays. In all the three cohorts, a significantly higher frequency of T allele and TT genotypes of ACACβ and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACACβ and C allele of AGTR1 were found to be significantly associated with proteinuria, a hallmark of DN. We also found significant epistatic interactions between these two genes. TT genotypes of ACACβ gene and CC genotype of AGTR1 gene confers the risk of DN and both genes had significant epistatic interaction in Asian Indian patients with T2DM.     

Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians

The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene.