Adipokine serum concentrations, anthropometric measurements and socio-economic status in two ethnic groups with different prevalence levels for cardiovascular diseases and type 2 diabetes

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9?ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52?pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5?cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.     

A radioenzymatic assay to identify three groups of phospholipase A(2) in platelets

Phospholipases A(2) (PLA(2)) are key enzymes in membrane metabolism. The release of fatty acids and lysophospholipids by PLA(2) activates several intra-cellular second messenger cascades that regulate a wide variety of physiological responses. The aim of the present study is to describe a radioenzymatic assay to determine the activity of three main PLA(2) subtypes in platelets, namely extracellular calcium-dependent PLA(2) (sPLA(2)) and intracellular calcium-dependent (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)). The differentiation of these distinct PLA(2) subtypes was based on the enzyme substrate preference (arachdonic acid or palmitoyl acid) and calcium concentration. Our results indicate that this new assay is feasible, precise and specific to measure the activity of the aforementioned subtypes of PLA(2). Therefore, this protocol can be used to investigate modifications of PLA(2) homeostasis in distinct biological models addressing the pathophysiology of many medical and neuropsychiatric disorders such as schizophrenia and Alzheimer's disease.     

Optimal initiation of insulin in type 2 diabetes

Treatment goals for glycemic control in patients with type 2 diabetes are often not achieved or are difficult to maintain as the disease progresses. Too often, insulin therapy is either delayed or is suboptimal. We discuss how the introduction of new insulin analogs may help overcome some of the barriers to insulin use. If combination therapy with oral agents does not achieve glycemic control, the addition of a once-daily intermediate- or long-acting insulin is a simple and highly effective strategy for initiating insulin. If glycemic control is still not achieved, a short- or rapid-acting insulin may be needed prior to meals (basal-prandial approach). A patient's baseline glycosylated hemoglobin (A1C) can guide whether glycemic control can be achieved with basal insulin or will require basal-prandial replacement. In addition to A1C, a patient's age, lifestyle, competence, personal preferences, and comorbidities can be used to help determine the choice of insulin therapy.     

Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups

Human narcolepsy-cataplexy, a sleep disorder associated with a centrally mediated hypocretin (orexin) deficiency, is tightly associated with HLA-DQB1*0602. Few studies have investigated the influence that additional HLA class II alleles have on susceptibility to this disease. In this work, 1,087 control subjects and 420 narcoleptic subjects with cataplexy, from three ethnic groups, were HLA typed, and the effects of HLA-DRB1, -DQA1, and -DQB1 were analyzed. As reported elsewhere, almost all narcoleptic subjects were positive for both HLA-DQA1*0102 and -DQB1*0602. A strong predisposing effect was observed in DQB1*0602 homozygotes, across all ethnic groups. Relative risks for narcolepsy were next calculated for heterozygous DQB1*0602/other HLA class II allelic combinations. Nine HLA class II alleles carried in trans with DQB1*0602 were found to influence disease predisposition. Significantly higher relative risks were observed for heterozygote combinations including DQB1*0301, DQA1*06, DRB1*04, DRB1*08, DRB1*11, and DRB1*12. Three alleles-DQB1*0601, DQB1*0501, and DQA1*01 (non-DQA1*0102)-were found to be protective. The genetic contribution of HLA-DQ to narcolepsy susceptibility was also estimated by use of lambda statistics. Results indicate that complex HLA-DR and -DQ interactions contribute to the genetic predisposition to human narcolepsy but that additional susceptibility loci are also most likely involved. Together with the recent hypocretin discoveries, these findings are consistent with an immunologically mediated destruction of hypocretin-containing cells in human narcolepsy-cataplexy.     

Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups

Background

To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.

Methods

1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.

Results

The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.

Conclusion

The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.     

Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study

In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using S_all statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance.     

Hypertriglyceridemic waist may explain ethnic differences in hypertension among patients with type 2 diabetes in Sweden

ABSTRACT: BACKGROUND: Hypertension is common among persons with type 2 diabetes. The aim of this study was to analyze the association between ethnicity and hypertension prevalence after adjusting for age, sex, Hba1c, total cholesterol, elevated triglycerides and hypertriglyceridemic waist. The study population consisted of 354 primary health care patients diagnosed with type 2 diabetes (173 Assyrians/Syrians and 181 Swedes) residing in Sodertalje, Sweden. Unconditional logistic regression was used to analyze the data. RESULTS: Hypertension prevalence was higher among Swedes than Assyrians/Syrians, (77% versus 58%; p = 0.001). In the unadjusted logistic regression model, the odds ratio for hypertension in Swedes was twice as high than that in Assyrians/Syrians (OR = 2.44; 95% CI =1.54 - 3.86). In the age- and sex-adjusted model, odds ratio of hypertension was 2.25 (95% CI 1.41-3.60). After adjustments for total cholesterol was made, the odds ratio of hypertension decreased slightly to 1.73. When elevated triglycerides and hypertriglyceridemic waist were separately introduced, the odds ratio of hypertension was no longer significant between the ethnic groups (1.60 and 1.43 for triglycerides and hypertriglyceridemic waist respectively). In addition, advanced age - 60-69 years old (OR = 1.80, CI 95% 1.00-3.20) and [greater than or equal to] 70 years old (OR = 2.88, CI 95% 1.40-5.93), elevated total cholesterol (OR = 1.48, CI 95% 1.12-1.95) and presents of hypertriglyceridemic waist (those with high WC and high TG) were significant confounding factors for the increased risk of hypertension independent of ethnicity. CONCLUSIONS: The crude differences in prevalence of hypertension between the Swedes and Assyrians/Syrians in our study population with type 2 diabetes were no longer significant when adjusting for high triglycerides levels or the presence of hypertriglyceridemic waist.     

Gene expression profiles of peripheral blood cells in type 2 diabetes and nephropathy in Asian Indians

Background  

Asian Indians with type 2 diabetes mellitus (T2D) have higher susceptibility to diabetic nephropathy (T2DN), the leading cause of end-stage renal disease and morbidity in diabetes. Peripheral blood cells (PBCs) play an important role in diabetes, yet very little is known about the molecular mechanisms of PBCs regulated in insulin homeostasis. In this study we explored the global gene expression changes in PBCs in diabetes and diabetic nephropathy to identify the potential candidate genes and molecular networks regulated in diabetes and nephropathy.     

DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group

Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed.We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.     

Type 1 and type 2 responses to Leishmania major

Pseudomonas aeruginosa and Burkholderia cepacia cause destructive lung disease in cystic fibrosis (CF) patients. Both pathogens employ 'quorum sensing', i.e. cell-to-cell communication, via diffusible N-acyl-L-homoserine lactone (AHL) signal molecules, to regulate the production of a number of virulence determinants in vitro. However, to date, evidence that quorum sensing systems are functional and play a role in vivo is lacking. This study presents the first direct evidence for the presence of AHLs in CF sputum. A total of 42 samples from 25 CF patients were analysed using lux-based Escherichia coli AHL biosensors. AHLs were detected in sputum from patients colonised by P. aeruginosa or B. cepacia but not Staphylococcus aureus. Furthermore, using liquid chromatography-mass spectrometry and thin layer chromatography, we confirmed the presence of N-hexanoylhomoserine lactone and N-(3-oxododecanoyl)homoserine lactone respectively in sputum samples from patients colonised by P. aeruginosa.     

KCNQ1 and type 2 diabetes: study in Hubei Han Chinese and meta-analysis in East Asian populations

Recent genome-wide association studies in East Asian poulations reported the association of KCNQ1 variants with type 2 diabetes. In the present study, we first investigated the association between rs2237892 in KCNQ1 and type 2 diabetes in a Hubei Han Chinese population (223 type 2 diabetes patients and 201 controls). The frequencies of CC genotype and C allele in type 2 diabetes patients were significantly higher than those of controls group (CC: 51.6% vs 39.3%, P=0.001; C: 72.2% vs 61.2%, P=0.001). The odds ratio for the risk allele C was 1.65 (95%CI 1.23–2.2, P=0.001). Then, we systematically reviewed the association of SNPs (rs2237892, rs2237895, rs2237897, rs2074196) in KCNQ1 with type 2 diabetes risk in a meta-analysis. Significant heterogeneity between studies was found for SNPs rs2237892 and rs2237897. Combined odds ratios of the rs2237892 C, rs2237895 C, rs2237897 C, rs2074196 G allele were 1.35 (95% CI 1.29–1.41, P<0.0001), 1.27 (95%CI 1.23–1.32, P<0.0001), 1.32 (95%CI 1.21–1.43, P<0.0001), 1.30 (95%CI 1.25–1.35, P<0.0001) respectively. Our results and meta-analysis demonstrated that KCNQ1 polymorphisms were reproducibly associated with the risk of type 2 diabetes in Han Chinese and East Asian populations.     

Simple anthropometric indices in relation to cardiovascular risk factors in Chinese type 2 diabetic patients

To determine which is the best anthropometric index among body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to height ratio (WHtR) in type 2 diabetic patients, we examined the relationship between these indices and cardiovascular risk factors using partial correlation analysis, chi-square test, logistic regression analysis and Receiver Operator Characteristic (ROC) curves. Partial correlation analysis showed that among the 4 obesity indices, WHtR had the highest r values for all the cardiovascular risk factors in both sexes, followed by WC. Chi-square analysis which revealed that an increased WHtR was more strongly associated with hypertension, hypertriglyceridemia (high TG) and low high-density lipoprotein cholesterol (HDL-C) than the other indices. Logistic regression analysis showed that, after controlling for age, the hypertension, high TG and low HDL-C odds ratios of WHtR > or = 0.5 were 2.56 (95% CI: 1.24, 5.29), 2.87 (95% CI: 1.43, 5.78), 2.59 (95% CI: 1.03, 6.59) in men and 3.75 (95% CI: 1.75, 8.05), 3.21 (95% CI: 1.52, 6.79), 3.62 (95% CI: 1.43, 9.21) in women, respectively. In ROC analysis, the areas under curve of WHtR were the largest for at least one risk factor in both men and women. These results indicated that WHtR had a higher correlation with cardiovascular risk factors than WC, WHR or BMI in newly diagnosed type 2 diabetes. We proposed the measurement of WHtR as a screening tool for cardiovascular risk factors in this population.     

Whole body bone,fat and lean mass in children: Comparison of three ethnic groups

We measured whole body bone, fat and lean mass, by dual-energy x-ray absorptiometry, of third-grade children in a suburban public school district adjacent to Detroit. Of 1,340 eligible children, 773 participated. Using U.S. Census categories, parents identified their children as black/African-American (57%), white (38%), or one of several other categories (5%). Some of the participants also identified with a relatively large Middle Eastern subgroup (Chaldeans). Of the 773 participants, 734 are included in this report (71 Chaldeans, 226 whites, and 437 black/African-Americans; other categories are omitted). We describe body size, body composition, and physical activity levels in the three groups. The Chaldean and black children have significantly higher average whole body bone mineral content (BMC) than whites (P > 0.05), but are not different from each other. Lean mass and height are significantly greater for Chaldeans and blacks than for whites. The ratio of BMC to height was also significantly greater in Chaldeans and blacks compared with whites. Chaldeans have a significantly higher weight and fat mass than either the black or white children, and report significantly less physical activity than either the white or the black children. The higher bone mass among the Chaldean children may be partially explained by their greater body mass, but there is no readily apparent explanation for the observed ethnic differences in body size. We cannot exclude genetic or environmental factors not evaluated in this observational study. Our unexpected finding that Chaldean children, when analyzed as a separate group, are more similar in body composition to black/African-American than to white children contributes to a growing body of literature indicating that the uncritical use of “race” categories may obscure rather than facilitate the identification of population differences. Am J Phys Anthropol 103:157–162, 1997. © 1997 Wiley-Liss, Inc.     

Restriction fragment length polymorphism (RFLP) at the DNF15S2 locus in three ethnic groups of Singapore

Three different ethnic groups from Singapore comprising 79 Chinese, 34 Malays and 23 Indians of Dravidian origin, were investigated for the HindIII RFLP at the DNF15S2 locus. The three populations had very similar allele frequencies and the frequency of rarer(S) allele was significantly (p less than 0.01) lower (0.21) in these ethnic groups compared to that in Caucasians (0.41). The phenotypic distributions were at Hardy-Weinberg equilibrium.