SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4, SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus, T2DM)的关系, 文章采用病例对照设计, 选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象, 应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法, 检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况, 比较T2DM组糖化血红蛋白(Hemoglobin A_1c, HbA_1c)在各基因型间的分布, 并进行单倍型分析。结果显示：①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs. 0.282, P =0.017); GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001; OR, 1.563; 95% CI, 1.189-2.053); 在显性模型(GG+GA vs. AA)分析中, G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P =0.002; OR, 1.525; 95% CI, 1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P >0.05)。②在T2DM组, rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA_1c水平, 但各基因型携带者之间HbA_1c水平并无统计学差异(P >0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1); 而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论：rs237025多态性与北京汉族人群T2DM的易感性相关, rs237024和rs600739多态性可能与T2DM的易感性不相关。     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4,SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus,T2DM)的关系,文章采用病例对照设计,选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象,应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法,检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况,比较T2DM组糖化血红蛋白(Hemoglobin A1c,HbA1c)在各基因型间的分布,并进行单倍型分析。结果显示:①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs.0.282,P=0.017);GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001;OR,1.563;95%CI,1.189-2.053);在显性模型(GG+GA vs.AA)分析中,G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P=0.002;OR,1.525;95%CI,1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P>0.05)。②在T2DM组,rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA1c水平,但各基因型携带者之间HbA1c水平并无统计学差异(P>0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1);而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论:rs237025多态性与北京汉族人群T2DM的易感性相关,rs237024和rs600739多态性可能与T2DM的易感性不相关。     

Role of chromium supplementation in Indians with type 2 diabetes mellitus

Type 2 diabetes mellitus is a complex metabolic disorder with adverse cardiovascular risk. The role of micronutrients has not yet been well clarified in this condition, especially in India.THE OBJECTIVES OF THIS STUDY WERE TO: (1) evaluate chromium status in Indian subjects with type 2 diabetes mellitus, (2) assess the effect of chromium picolinate (200 &mgr;g trivalent chromium twice daily) administration on glycaemic control and lipid profile in these subjects and (3) comment on the possible mechanism of any beneficial effect noted above.Fifty subjects were studied in a double blind, placebo-controlled, crossover fashion, with each treatment arm (chromium/placebo) lasting 12 weeks and 4 weeks' wash-off period in between. 50 healthy age- and sex-matched volunteers served as controls. Serum chromium level appeared to be higher in the general population in our country compared to western countries (36.5-59.5 nmol/L as compared to 2.3-40.3 nmol/L) However, the local diabetics were found to have a lower serum chromium level than the healthy controls (32.3 nmol/L against 44.7 nmol/L; p < 0.0001) and a mean increase of 3.5 nmol/L was noted after 12 weeks of chromium supplementation that was, expectedly, not seen in the placebo phase (p < 0.0001).Significant improvement in glycaemic control was noted in the chromium-treated group (DeltaFasting serum glucose = 0.44 mmol/L, p < 0.001; DeltaPost-prandial serum glucose = 1.97 mmol/L, p < 0.001; Deltaglycated hemoglobin = 0.01; p = 0.04, in comparison to placebo) This was accompanied by a significant greater fall in fasting serum insulin in the chromium-treated group, p < 0.05.The change in lipid parameters (total serum cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides) did not show significant difference between the chromium and placebo groups.Clinically significant hematological, renal or hepatic toxicity were excluded by routine hemogram, serum urea, creatinine, alanine amino transferase (ALT) and alkaline phosphatase estimations.In conclusion, chromium supplementation seems to improve glycaemic control in type 2 diabetic patients, which appears to be due to an increase in insulin action rather than stimulation of insulin secretion.     

Association of insulinase gene polymorphisms with type 2 diabetes mellitus in patients from the Moscow population

Association of 13 single nucleotide polymorphisms (SNPs) of insulinase (IDE) gene with type 2 diabetes mellitus (T2D) in the Moscow population has been examined. Three polymorphic markers (rs7078413, rs7899603, and rs551266) associated with the risk of T2D development have been revealed. Allele and genotype frequency distribution for these three markers differed significantly only in the sample of females between T2D patients and control individuals, while only in case of rs7078413 SNP genotype frequencies varied significantly in the total population.     

Association study of the ABCC8 gene variants with type 2 diabetes in south Indians

BACKGROUND:

The ABCC8 gene which encodes the sulfonylurea receptor plays a major role in insulin secretion and is a potential candidate for type 2 diabetes. The -3c → t (rs1799854) and Thr759Thr (C → T, rs1801261) single nucleotide polymorphisms (SNPs) of the ABCC8 gene have been associated with type 2 diabetes in many populations. The present study was designed to investigate the association of these two SNPs in an Asian Indian population from south India.

MATERIALS AND METHODS:

A total of 1,300 subjects, 663 normal glucose tolerant (NGT) and 637 type 2 diabetic subjects were randomly selected from the Chennai Urban Rural Epidemiology Study (CURES). The -3c → t and Thr759Thr were genotyped in these subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and a few variants were confirmed by direct sequencing.

RESULTS:

The frequency of the ‘t’ allele of the -3c → t SNP was found to be 0.27 in NGT and 0.29 in type 2 diabetic subjects (P = 0.44). There was no significant difference in the genotypic frequency between the NGT and type 2 diabetic group (P = 0.18). Neither the genotypic frequency nor the allele frequency of the Thr759Thr polymorphism was found to differ significantly between the NGT and type 2 diabetic groups.

CONCLUSION:

The -3c → t and the Thr759Thr polymorphisms of the ABCC8 gene were not associated with type 2 diabetes in this study. However, an effect of these genetic variants on specific unidentified sub groups of type 2 diabetes cannot be excluded.     

Candidate gene polymorphisms among North Indians and their association with schizophrenia in a case-control study

Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A number of candidate genes, a majority of them from the monoaminergic pathway in the brain, have been very popular in association studies with schizophrenia, a neuropsychiatric disorder. In this study diallelic/multiallelic polymorphisms in some dopaminergic, serotonergic and membrane-phospholipid-related genes have been evaluated in a control population recruited from North India. Association, if any, of these allelic variants with schizopherenia has been tested using a case-control approach. The case data have been taken from our published family-based association studies in schizophrenia. Of the eight genes tested in this study, association with schizophrenia was observed for only two gene polymorphisms, one in the promoter region of the serotonin 2A receptor gene and the other in the tryptophan hydroxylase gene. One new allele for the dopamine transporter gene (with eight repeats, 570-bp size), not reported in any population so far, has been identified in one individual in our sample. The data generated in this study, besides providing a normative background for various disease association studies, are a significant contribution to the population-specific genome database, a currently growing requirement.     

Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population

Type 1 diabetes mellitus (T1DM) is one of the T-cell mediated autoimmune diseases and vitamin D suppresses activation of T-cell and has immunomodulatory effects. In this study the association between four vitamin D receptor (VDR) gene polymorphisms, at positions FokI, BsmI, ApaI and TaqI, and susceptibility to T1DM was investigated. We assessed 87 Iranian patients with T1DM and one hundred healthy controls with no history of diabetes or other autoimmune diseases. Our results demonstrated that genotypes frequency of the TaqI VDR polymorphism differed significantly between T1DM patients and controls, TT genotype and T allele was more frequent in healthy controls compared with TIDM patients (P = 0.003; OR = 0.51, 95% CI = 0.31–0.84). Therefore, allele t is the risk-allele for developing TIDM in this study. No significant association was observed between others VDR SNPs and disease susceptibility. In conclusion, our case-control study indicated that the VDR TaqI polymorphism is associated with TIDM in Iranian population.     

Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population

Background

To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.

Methodology/Principal Findings

In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK) were genotyped using TaqMan allelic discrimination assays. The genotype and allele distributions of each SNP between the GDM cases and controls and the combined effects of alleles for the risk of developing GDM were analyzed. We found that the rs4402960, rs2383208 and rs391300 were statistically associated with GDM (OR = 1.207, 95%CI = 1.029–1.417, p = 0.021; OR = 1.242, 95%CI = 1.077–1.432, p = 0.003; OR = 1.202, 95%CI = 1.020–1.416, P = 0.028, respectively). In addition, the effect was greater under a recessive model in rs391300 (OR = 1.820, 95%CI = 1.226–2.701, p = 0.003). Meanwhile, the joint effect of these three loci indicated an additive effect of multiple alleles on the risk of developing GDM with an OR of 1.196 per allele (p = 1.08×10⁻⁴). We also found that the risk alleles of rs2383208 (b = −0.085, p = 0.003), rs4402960 (b = −0.057, p = 0.046) and rs10830963 (b = −0.096, p = 0.001) were associated with HOMA-B, while rs7754840 was associated with decrease in insulin AUC during a 100 g OGTT given at the time of GDM diagnosis (b = −0.080, p = 0.007).

Conclusions/Significance

Several risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. The effects of these SNPs on GDM might be through the impairment of beta cell function and these risk loci contributed additively to the disease.     

Association analysis of TNFRSF1B polymorphisms with type 2 diabetes and its related traits in North India

Inflammation plays a crucial role in the pathogenesis of type 2 diabetes and various lines of evidences suggest an important contribution of type 2 receptor for TNFα (TNFR2), a mediator of inflammatory responses. Though genetic association of TNFRSF1B (encoding TNFR2) polymorphisms have been investigated in various studies, their involvement is not clear because of inconsistent findings. Because of high susceptibility of Indian population to type 2 diabetes and its complications, we evaluated the association of TNFRSF1B polymorphisms-rs1061622 (M196R; exon6) and rs3397 (3′UTR) and (CA) _n repeat (intron 4) in 1,852 subjects including 1,040 cases and 812 controls with type 2 diabetes and its associated peripheral neuropathy and hypertension in North Indians of Indo-European ethnicity. The allelic and genotypic distributions of these polymorphisms were comparable among healthy control vs. type 2 diabetes, peripheral neuropathy vs. non-neuropathy and hypertensive vs. normotensive groups. (CA) _n polymorphism has been shown to be associated with diabetic neuropathy in Caucasians, however, this could not be replicated in our study (P = 0.27). None of the polymorphisms were found to influence the 14 anthropometric and biochemical traits related to type 2 diabetes studied here. Thus, we conclude that TNFRSF1B is not a major contributing factor to the genetic risk of type 2 diabetes, its associated peripheral neuropathy and hypertension and related metabolic traits in North Indians.     

Association of trace metal elements with lipid profiles in type 2 diabetes mellitus patients: a cross sectional study

Background

It is well known that dyslipidemia and chronic hyperglycemia increase the onset of diabetes and diabetic complication. The aim of this study is to see the association of trace metals elements and lipid profile among type 2 diabetes mellitus patients.

Methods

The study was conducted on 214 type 2 diabetic patients at Jimma University Specialized Hospital, Jimma, Ethiopia. All the eligible study participants responded to the structured interviewer administered questionnaire and fasting venous blood was drawn for biochemical analysis. Trace metal elements (zinc(Zn⁺²), magnesium(Mg⁺²), chromium(Cr⁺³), calcium(Ca⁺²), phosphorus(Po₄ ^?3), manganese(Mn⁺²), copper(Cu⁺²), and iron(Fe⁺³)) and lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), and triglycerides (TG)) were measured by atomic absorption spectrophotometry and enzymatic determination method respectively. Data were analyzed by SPSS version 24 software for windows. Bonferroni correction for multiple statistical comparisons was used and a p-value less than 0.01 were accepted as a level of significance.

Result

The mean age of study participants was 42.95(±12.6) with an average of 5.83(±3.1) years being diagnosed with diabetes mellitus. The BMI of female (27.1(±4.9)) was significantly higher than male (25.21(±4.2)). BMI shows positive and significant (p < 0.01) association with lipid profiles (TC, LDL-C, and TG) among type 2 diabetic patients in the liner regression model. In addition, WH-R was positively associated with TG. In Pearson partial correlation adjusted for sex and age, Za⁺² shown to have statistically significant and negative correlations with TC, LDL-C and with TG. Mg⁺² and Cr⁺² negatively and significantly correlated with the lipid profile TC and LDL-C. Ca⁺² negatively correlated with TC and TG. Po^?3 ₄ positively correlated with HDL-C; iron negatively correlated with TC. However, in the liner regression model, only calcium positively and significantly (Beta = ?0.21, p < 0.01) associated with TG.

Conclusion

In the current study, a negative correlation was observed between trace metal elements (Zn⁺², Mg⁺², Cr⁺³, Ca⁺² and Fe⁺³) and lipid profile (TC, LDL-C and TG) among type 2 diabetes mellitus patients. In addition, Ca⁺² observed to be associated with TG. Future studies are highly advised to uncover the bidirectional association between trace metal element and dyslipidemia in diabetic patients.

     

Association of RAGE gene polymorphisms with type 2 diabetes mellitus,diabetic retinopathy and diabetic nephropathy

A meta-analysis was performed to assess the associations of the receptor for advanced glycation end products (RAGE) gene polymorphisms [Gly82Ser (rs2070600), 1704 G/T (rs184003), 429 T/C (rs1800625)] with type 2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and diabetic nephropathy (DN). A comprehensive research was conducted to identify all case-control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Peters test. Twenty-nine articles were included. Overall, after excluding articles deviating from Hardy–Weinberg equilibrium in controls and sensitive analysis, no significant association was found between RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) and any of T2DM, DR and DN risk, respectively. Subgroup analysis stratified by ethnicity (Asian and Caucasian) also found no significant association between the above-mentioned three polymorphisms and T2DM risk, respectively. This meta-analysis suggested that there might be no association of RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) with T2DM, DR and DN risk.     

Association of SGK1 gene polymorphisms with type 2 diabetes

The serum and glucocorticoid inducible kinase SGK1 is genomically upregulated by glucocorticoids and in turn stimulates a variety of carriers and channels including the renal epithelial Na(+) channel ENaC and the intestinal Na(+) glucose transporter SGLT1. Twin studies disclosed an association of a specific SGK1 haplotype with moderately enhanced blood pressure in individuals who are carrying simultaneously a homozygous genotype for a variant in intron 6 [I6CC] and a homozygous or heterozygous genotype for the C allele of a polymorphism in exon 8 [E8CC/CT] of the SGK1 gene. A subsequent study confirmed the impact of this risk haplotype on blood pressure. SGK1 knockout mice are resistant to the insulin and high salt induced increase of blood pressure, glucocorticoid induced increase of electrogenic glucose transport, and glucocorticoid induced suppression of insulin release. The present study explored whether the I6CC/E8CC/CT haplotype impacts on the prevalence of type 2 diabetes. The prevalence of the I6CC genotype was 3.1% in a healthy German, 2.4 % in a healthy Romanian and 11.6 % in a healthy African population from Ghana (p=0.0006 versus prevalence in Caucasians). Comparison of genotype frequencies between type 2 diabetic patients and the respective control groups revealed significant differences for the intron 6 T>C variant. Carriers of at least one T allele were protected against type 2 diabetes (Romanians: p=0.023; OR 0.29; 95% CI 0.09-0.89; Germans: p=0.01; OR 0.37; 95% CI 0.17-0.81). The SGK1 risk haplotype (I6CC/E8CC/CT) was significantly (p=0.032; OR 4.31, 95% CI 1.19-15.58) more frequent in diabetic patients (7.2 %) than in healthy volunteers from Romania (1.8%). The observations support the view that SGK-1 may participate in the pathogenesis of metabolic syndrome.     

Association study of promoter polymorphisms in the CETP gene with longevity in the Han Chinese population

The cholesteryl ester transfer protein (CETP), which is involved in the regulation of reverse cholesterol transport and metabolism of high-density lipoprotein cholesterol, has been proposed as a candidate gene for human longevity. SNPs in the promoter region of the CETP gene is likely important in regulation of the expression of the CETP gene. To explore the potential effects of the promoter polymorphisms in the CETP gene on longevity, we investigated the promoter polymorphisms in a sample of long-lived (≥90 years old) Han Chinese collected from Southwestern China (N = 380). By resequencing 934 bp of the promoter region, genotypes of four SNPs (?573A/G, ?629A/C, ?971A/G, ?1046T/C) were examined in this sample. However, no association could be confirmed between longevity and these SNPs or haplotypes inferred from them. A novel rare variant ?573A/G was found and was found in heterozygote state only in five persons in the Longevity group. But it was not statistically significant (p = 0.075). We also examined this novel polymorphism ?573A/G in another Han Chinese sample from Yunnan province, and it was not associated with longevity. The results from both samples suggest that there is likely no association of the CETP gene promoter polymorphisms with longevity, at least among Han Chinese.     

线粒体基因组D-Loop区基因多态性与2型糖尿病的相关性

随机选取199例浙江地区2型糖尿病患者与102例正常对照, 采用聚合酶链反应(Polymerase chain re-action, PCR)、基因片段直接测序来检测线粒体基因组D-Loop区域基因变异情况, 同时分析其与主要临床指标的关系。结果显示: 线粒体基因组D-Loop区域为一高变异区, np73A-G、np263A-G、np16223C-T、np16519T-C为4个高变异位点; 发现29个未见报道的新变异位点; np193A-G、np234A-G、np16108C-T等变异与糖尿病家族史有关。这表明浙江籍汉族人线粒体基因组D-Loop区存在大量基因多态性现象, 此区域的某些变异可能与糖尿病的发生发展等具有一定相关性。     

Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals

A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093–1.188), 1.177 (1.099–1.259) and 1.207 (1.094–1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.     

Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor (IR) dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) with lipids, proteins and other molecules of the human body. Production of RMs mainly superoxides (•O₂⁻) has been found in a variety of predominating cellular enzyme systems including nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, endothelial nitric oxide synthase (eNOS) and myeloperoxidase. The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product formation; activation of protein kinase C isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and NOS are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in the pathogenesis of T2DM. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiates stress related pathways thereby leading to IR and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.     

An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians.

Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q.     

Heat shock protein 70 and albuminuria in patients with type 2 diabetes: a matched case control study

Here, we aimed to study serum heat shock protein (HSP) 70 levels in diabetic patients with and without albuminuria. We performed a 1:1 matched case control study on 40 diabetic patients with albuminuria as cases and 40 age, sex, body mass index matched diabetic patients without albuminuria (normoalbuminuria) as controls. Normoalbuminuria was defined as urinary albumin excretion rate <15 mg/12 h, and albuminuria was defined as urinary albumin excretion rate between 100–400 mg/12 h. Patients with albuminuria had a higher HSP70 than controls (0.83 ± 0.50 vs. 0.63 ± 0.06; p = 0.02), while they did not differ in any other studied variables. In ten of the studied pairs, the controls had higher HSP70 levels than cases (reverse relationship). Patients in the “direct relationship group” had higher HbA1c values than the patients in the “reverse relationship group” (8.9 ± 0.3 vs. 7.3 ± 0.6, p = 0.04). Cases in the reverse pairs had a lower low density lipoprotein cholesterol levels than their controls. The odds ratio of HSP70 in the prediction of albuminuria was (28.69 (3.2–250.1), p = 0.002). In conclusion, we have shown an increased HSP70 levels in diabetic patients with albuminuria.