SLC30A8 polymorphism and type 2 diabetes risk: Evidence from 27 study groups

Background and aims

Intense research has been performed to identify the genetic risk factors in type 2 diabetes, and a single nucleotide polymorphism (SNP) in SLC30A8 (rs13266634) was reported to be associated with type 2 diabetes mellitus. However, published data on the association between SLC30A8 polymorphism and the risk of type 2 diabetes were inconsistent. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship.

Methods and results

We searched PubMed through October 2009 to identify all relevant papers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted under an additive genetic model. In the current meta-analysis, we identified a total of 27 groups including 42,609 cases and 69,564 controls. In analyses of the case-control studies by ethnicity, the results indicated that SLC30A8 polymorphism was related to elevate risks of type 2 diabetes both in Europeans (OR = 1.15, 95% CI 1.11-1.18, P < 0.001) and Asians (OR = 1.15, 95% CI 1.11-1.19, P < 0.001). Next, we separated hospital-based case-control studies from population-based case-control studies, however, there was no apparent difference between population-based case-control study groups (OR = 1.15, 95% CI 1.12-1.17, P < 0.001) and hospital-based case-control study groups (OR = 1.16, 95% CI 1.07-1.25, P < 0.001).

Conclusion

Our present meta-analysis provided evidence that SLC30A8 (rs13266634) C allele carriers could elevate the risk of type 2 diabetes, especially in Europeans and Asians.     

Association of the cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G/T) polymorphism with phenotypes of metabolic syndrome in a Chinese population

Aims

The CIDEA gene is involved in energy metabolism and a non-synonymous single nucleotide polymorphism (SNP), V115F (G/T), is a risk factor for obesity in Swedish subjects and metabolic syndrome (MetS) in Japanese subjects. However, the risk allele was a G in Swedish subjects and a T in Japanese subjects. The present study investigated the association between this SNP and MetS in a Chinese population.

Methods

Three hundred and fifty-one subjects evaluated at the Cardiac Clinic in Xuanwu Hospital for MetS risks were recruited. Anthropometric measurements, blood pressure, fasting blood glucose, and blood lipid levels were determined in addition to the polymorphism.

Results

The proportion of subjects with MetS was significantly higher based on genotype, in the order: GG < GT < TT (p = 0.003). In multiple logistic regression analysis, the odds ratios for MetS in the GT and TT genotypes, compared to the referent GG genotype, were 2.26 (p = 0.003) and 2.89 (p = 0.002), respectively. Similar trends were observed for the related phenotypes of central obesity (GT: OR = 2.20, p = 0.004; TT: OR = 3.31, p = 0.002) and dyslipidemia (GT: OR = 1.73, p = 0.047; TT: OR = 2.10, p = 0.03).

Conclusions

The T allele of the CIDEA V115F SNP is a risk factor for MetS and its related phenotypes in a Chinese population.     

The G3057A LEPR polymorphism is associated with obesity in Tunisian women

Objectives

The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population.

Design and methods

Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ² = 4.90, p = 0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA + AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ² = 4.08, p = 0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR = 2.73, 95% CI 1.03-7.21) and for carriers of GA + AA genotypes (OR = 1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations.

Conclusion

There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.     

Association between rs13266634 C/T polymorphisms of solute carrier family 30 member 8 (SLC30A8) and type 2 diabetes, impaired glucose tolerance, type 1 diabetes--a meta-analysis

Aims

To investigate the association of solute carrier family 30 member 8 (SLC30A8) rs13266634 C/T polymorphism with type 2 diabetes (T2DM), impaired glucose tolerance (IGT), and type 1 diabetes (T1DM).

Methods

We searched all the publications about the association between SLC30A8 and diabetes from PubMed, and evaluated the association between SLC30A8 rs13266634 C/T polymorphism and T2DM, IGT and T1DM, respectively, by meta-analysis of all the validated studies. Allelic and genotypic comparisons between cases and controls were evaluated.

Results

Thirty six studies were included in the meta-analysis: 31 studies were analysed for rs13266634 C/T polymorphism with T2DM, 3 studies with IGT and 4 studies with T1DM. The pooled odds ratios (ORs) for allelic and genotypic comparisons (including additive model, co-dominant model, dominant model and recessive model) showed that rs13266634 C/T polymorphism was significantly associated with increased T2DM risk: OR = 1.15, 95% confidence interval (CI) = 1.13-1.17, P < 0.001, P_{heterogeneity} = 0.041, OR = 1.34, 95% CI = 1.26-1.41, P < 0.001, P_{heterogeneity} = 0.908, OR = 1.20, 95% CI = 1.16-1.24, P < 0.001, P_{heterogeneity} = 0.699, and OR = 1.23, 95% CI = 1.17-1.30, P < 0.001, P_{heterogeneity} = 0.801, respectively. In subgroup analyses, we found that rs13266634 C/T polymorphism was associated with T2DM risk both in Asian and European subgroup (P < 0.001), but not in African (P > 0.05). And the pooled odds ratio (OR) for allelic frequency comparison showed that rs13266634 C/T polymorphism was also significantly associated with IGT: OR = 1.15, 95% CI = 1.06-1.26, P < 0.001, P_{heterogeneity} = 0.364. Meanwhile, our meta-analysis did not suggest that rs13266634 C/T polymorphism was associated with T1DM risk (P > 0.05): OR = 1.02, 95% CI = 0.98-1.06, P = 0.328, P_{heterogeneity} = 0.488 for allelic frequency comparison.

Conclusions

Our meta-analysis results revealed the significant association between rs13266634 C/T polymorphism and T2DM and IGT, but did not support the association between this polymorphism and T1DM.     

VEGF gene polymorphism association with diabetic foot ulcer

Objective

Functional polymorphisms within vascular endothelial growth factor (VEGF) gene have shown association with various conditions including diabetic neuropathy and retinopathy. In this study we have performed a candidate gene association study in order to examine VEGF gene polymorphism association with diabetic foot ulcer (DFU).

Methods

The study group comprised of type 2 diabetes patients with (N = 247) and without (N = 241) DFU. Healthy control subjects (N = 98) were also recruited from the same area. The ARMS-PCR technique was applied for genotyping of VEGF gene SNPs at positions −7*C/T and −2578*C/A.

Results

The frequency of genotype AA was significantly decreased in patients with DFU compared with diabetic subjects without DFU (AA vs CA + CC, p = 0.003, OR = 0.44, CI = 0.24-0.80). Also there was a significant decrease in frequency of A allele in patients with DFU compared to the controls (p = 0.02, OR = 0.68, CI = 0.48-0.96).

Conclusion

It seems that lower frequency of A allele in patients with DFU is conferring a protective effect which might be as a result of increased angiogenesis in patients carrying this allele.     

Effect of statin therapy on contrast-induced nephropathy after coronary angiography: a meta-analysis

Background

Although the pleiotropic effects of statins are postulated to be renoprotective, clinical studies have demonstrated conflicting results. We undertook a meta-analysis of published trials to evaluate the impact of statin therapy on the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography.

Methods

We searched MEDLINE and EMBASE databases through December 2010 for articles evaluating the effect of statins on the incidence of CIN in patients undergoing coronary angiography. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using random effects modeling.

Results

Three randomized controlled trials involving 770 patients (330 in the statin group and 340 in the control group) and 7 non-randomized studies involving 31,959 patients (11,936 statin-pretreated and 20,023 statin-naïve). The definition of CIN varied somewhat among the studies. Based on the pooled estimate across the 3 randomized controlled trials, statin therapy did not significantly reduce the incidence of CIN compared to control (OR = 0.76, 95% CI: 0.41-1.41, p = 0.39). No significant heterogeneity was found in the randomized studies (I² = 0%, p = 0.48). The pooled analysis of the non-randomized studies showed a marginally significant benefit associated with statin therapy (OR = 0.60, 95% CI: 0.36-1.00, p = 0.05). There was significant heterogeneity among the non-randomized studies (I² = 88%, p < 0.00001).

Conclusions

Our meta-analysis suggests that statin therapy might be associated with a significant reduction in the incidence of CIN in patients undergoing coronary angiography. Further studies are warranted to clarify this issue.     

Reliability and validity of diabetes specific Health Beliefs Model scales in patients with diabetes and serious mental illness

Objective

To study the association of low serum creatinine, abnormal lipid profile and demographic variables with type 2 diabetic Trinidadian subjects.

Methods

Data were obtained from a cohort of 1122 diabetic and non-diabetic patients from clinics in Trinidad. Variables measured included demographics, HbA1_c, serum creatinine, lipid profile values and diabetic status.

Results

The sample consisted of 476 males (61.6% diabetic) and 646 females (50.3% diabetic). Most patients (59.2%) were Indo-Trinidadian, 23.4% were Afro-Trinidadian and 13.5% were of ‘mixed’ and ‘other’ categories. The majority (55.1%) of the patients were diabetic and diabetics were older than non-diabetics (p = 0.000). Abnormal lipid profile OR = 0.728, CI (0.532, 0.994), serum creatinine categories OR = 1.520, CI (1.317, 1.754), gender OR = 0.690, CI (0.533, 0.892) and age groups OR = 1.305, CI (1.185, 1.437) were useful predictors of type 2 diabetes. Ethnicity was not a useful predictor: OR = 1.007, CI (0.869, 1.168). Serum creatinine (mean) was found to be lower in diabetics aged 21-50 than in their non-diabetic counterparts. However, above 50 years old, the reverse was true. Serum creatinine means were higher in males than in females (p = 0.000).

Conclusion

Abnormal lipid profile, gender, age and serum creatinine are associated with type 2 diabetes. While age and gender are non-modifiable risk factors, steps should be taken to monitor and control the serum creatinine and lipid profile values of diabetics and non-diabetics.     

Association of angiotensin II type 1 receptor gene A1166C polymorphism with the presence of diabetes mellitus and metabolic syndrome in patients with documented coronary artery disease

Background

There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT₁R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients.

Methods

Patients with angiographically defined coronary artery disease (CAD) (n = 309) were evaluated for the presence of AT₁R/A1166C polymorphism. These patients were classified into subgroups with (n = 164, M/F: 109/55) and without (n = 145, M/F: 84/61) diabetes mellitus. The AT₁R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method.

Results

There was a higher frequency of polymorphic genotypes (AC + CC) in the diabetic compared with the non-diabetic group (p = 0.01). When determined for each gender separately, this difference remained significant in the males (p = 0.04) but not in females (p = 0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p = 0.01). This remained significant after gender segregation for males (p = 0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (β = 1.16, p < 0.001 for total population and β = 1.29, p < 0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p = 0.04).

Conclusion

The AT₁R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD.     

Association of Taq 1B CETP polymorphism with insulin and HOMA levels in the population of the Canary Islands

Background and aims

Cholesteryl ester transfer protein (CETP) is an enzyme with a key role in lipoprotein metabolism. A common genetic polymorphism, the Taq 1B, influences CETP activity and HDL-cholesterol levels, with individual homozygotes for the B1 allele exhibiting higher enzyme activity and lower HDL-cholesterol levels than carriers of at least one B2 allele. Our aim was to analyze the influence of Taq 1B CETP polymorphism on cardiovascular risk factors in a representative sample of adult subjects from Canary population.

Methods and result

A total of 518 adult subjects from the Canary Islands, enrolled in a nutritional survey (the ENCA study), were included. The Taq 1B polymorphism was analyzed by PCR-RFLP. Compared with individuals with at least one B2 allele, and after adjusting for age, sex, BMI, waist perimeter, smoking and alcohol intake, carriers of the B1B1 genotype showed lower HDL-cholesterol levels (geometric mean (95% CI): 46.6 (44.5-48.8) vs. 50.6 (49.1-52.9) mg/dl; P = 0.003); and higher insulin (geometric mean (95% CI): 11.1 (10.5-11.9) vs. 10.0 (9.5-10.5 μU/ml; P = 0.008) and HOMA levels (geometric mean (95% CI): 2.3 (2.1-2.5) vs. 2.1 (1.9-2.1); P = 0.009). In addition, the B1B1 genotype was more frequent in individuals who had low levels of HDL-cholesterol according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (Odds Ratio (OR): 1.563; 95% CI: 1.04-2.34; P = 0.030), and in those included in the upper quartile of insulinemia (OR: 1.90; 95% CI: 1.20-3.03; P = 0.007) and HOMA (OR: 1.61; 95% CI: 1.02-2.57; P = 0.043).

Conclusion

The observed influence of Taq 1B polymorphism on insulin levels and HOMA highlights the possible role of CETP in the regulation of glucose homeostasis.     

Type 2 diabetes does not attenuate racial differences in coronary calcification

Aims

Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD.

Methods

Multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes.

Results

AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p < 0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p = 0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p = 0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p = 0.055)] partially attenuated the association in women.

Conclusions

Relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors.     

Influence of glycosylated hemoglobin on sight-threatening diabetic retinopathy: a population-based study

Aim

To evaluate the role of glycosylated hemoglobin (HbA1c) on the occurrence of sight-threatening diabetic retinopathy (STDR) in urban Chennai, Tamil Nadu, India.

Methods

A total of 5999 individuals were enumerated from the Chennai metropolis. Of these, 1414 subjects with diabetes were included for data analysis in the study. STDR or non-STDR groups were classified based on the fundus photographs. HbA1c was measured (Bio-Rad DiaSTAT™ HbA1c Reagent Kit) by the liquid chromatography technique.

Results

A statistically significant difference (p < 0.05) was noted in the duration of diabetes, gender, body mass index, HbA1c, micro- and macro-albuminuria between both non-STDR and STDR groups as compared to the no-diabetic retinopathy (DR) group. On multivariate analysis, HbA1c (non-STDR: odd's ratio OR = 1.23; 95% confidence interval CI = 1.15-1.32; p < 0.0001; STDR: OR = 1.31 95% CI = 1.14-1.52; p < 0.0001) was found to be significantly associated with non-STDR and STDR when compared with the no-DR group. The Receiver Operating Characteristic analysis showed that the cut-off value of 8.0 had 75.6% sensitivity and 58.2% specificity with 64.9% maximum area under the curve.

Conclusion

HbA1c value >8.0% was significantly related with STDR. In a screening programme, the cut-off value of HbA1c >8.0% provided a maximum yield of STDR.     

Inflammatory status, arterial stiffness and central hemodynamics in hypertensive patients with metabolic syndrome

Introduction

Inflammatory state is activated in metabolic syndrome and may explain part of the adverse prognosis of this entity. Arterial stiffness, central blood pressures and wave reflections are independent predictors of cardiovascular risk. This study investigates the relation between low-grade inflammation and arterial stiffness and central hemodynamics in patients with metabolic syndrome.

Methods

We studied 106 consecutive hypertensive patients with metabolic syndrome. Arterial stiffness was assessed by carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV). Central blood pressures were evaluated by pulse wave analysis and heart rate corrected augmentation index (AIx₇₅) was used as a measure of wave reflections. White blood cell count (WBC), high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured as inflammatory markers.

Results

In univariable analysis, PWVc-f correlated with both hsCRP (p < 0.01) and fibrinogen (p < 0.01), while PWVc-r correlated with hsCRP (p = 0.05). Regarding central blood pressures, aortic SBP correlated positively with hsCRP (p < 0.05) and marginally with fibrinogen (p = 0.06) and WBC (p = 0.08). Interestingly, no correlation was found between AIx₇₅ and any of these biomarkers. After adjustment for age, gender, smoking, mean arterial pressure, heart rate, waist circumference, glucose, total and HDL cholesterol, PWVc-f was independently related to hsCRP (p < 0.001) and fibrinogen (p < 0.01), while a marginal independent correlation was also found between PWVc-r and hsCRP (p = 0.06). Furthermore, aortic PP independently associated with fibrinogen (p < 0.05) whereas marginal associations demonstrated between aortic SBP and hsCRP and fibrinogen (p = 0.06 for both).

Conclusion

Inflammatory status is related to arterial stiffness and central blood pressures (but not to augmentation index) in hypertensives with metabolic syndrome. These findings may have implications for increased cardiovascular risk in these patients.     

Associations des facteurs environnementaux avec le risque de la maladie coronaire à Tlemcen (Algérie)

Purpose

In the purpose of studying the effect of the environmental factors on risk of coronary artery disease, we established a case-control study in Tlemcen.

Method and results

A sample of 568 men and women aged 25 to 64 years, was studied; 170 had had myocardial infarction or angina and 398 controls. Variables associated with CAD were age, sex, tobacco consumption, hypertension, diabetes, obesity, family history of cardiovascular disease, total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol. Adjusted odds-ratio and their 95 % CIs were calculated by logistic regression. Hypertension (OR = 2.48 [1.68; 3.67]), diabetes (OR = 2.86 [1.89; 4.34]), obesity (OR = 1.21 [0.76; 1.92]), family history of cardiovascular disease (OR = 3.49 [1.39; 8.73]), total cholesterol (OR = 0.99 [0.51; 1.92]), triglycerides levels (OR = 1.76 [0.93; 3.35]), HDL-cholesterol (OR = 2.48 [1.69; 3.66]) and LDL-cholesterol (OR = 1.09 [0.59; 2.01]). The variables differing most significantly and independently between cases and controls were identified by stepwise logistic regression analysis (p < 0.05), variables concerned hypertension and diabetes (p < 0.0001), decrease HDL-cholesterol (p = 0.0002) and tobacco consumption (p = 0.005), with stronger associations in cases than in controls.

Conclusion

It is concluded that hypertension and diabetes, decrease HDL-cholesterol in both sexes, an increase in concentration of triglyceride only in women and tobacco consumption in men, were significantly related to coronary artery disease in Tlemcen.     

The obesity gene and colorectal cancer risk: a population study in Northern Italy

Background

Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity.

Aims

To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population.

Patients and methods

1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F = 197/144, mean age = 65.17 ± 11.16 years), colorectal adenoma (385 pts., M/F = 247/138, mean age = 62.49 ± 13.01 years), healthy controls (311 pts., M/F = 150/161, mean age = 57.31 ± 13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR.

Results

The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR = 1.106; CI 95% = 0.788-1.550; p = 0.561) or colorectal adenomas (OR = 0.830; CI 95% = 0.602-1.144; p = 0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI.

Conclusion

The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.     

Myonecrosis and inflammatory response following percutaneous coronary angioplasty. A protective role for betablockers?

Introduction

Percutaneous coronary intervention (PCI) is widely used actually for the treatment of coronary disease. Stent implantation in the vessel wall is associated with local healing processes and some myonecrosis. However, little is known about the relationships between systemic inflammatory response, myonecrosis and the patient's and procedural characteristics.

Objectives

(i) To evaluate the level of C-Reactive Protein (hsCRP) and cardiac troponin I (cTnI) elevation after PCI; (ii) to determine the patient's and procedural factors associated with those elevations.

Method

This is a prospective monocentric study carried out in patients hospitalised for elective PCI or for ACS without cTnI elevation. CRP and cTnI were assessed before, after and 24 hours after the procedure.

Results

Thirty-four patients (mean age 64 ± 10.9 years; sex ratio 28 males/six females) were included. hsCRP increased in 26 patients (76.4%) and cTnI in 16 patients (47%) after PCI. cTnI elevation did not correlate with inflammatory response. Whereas none of the studied parameters were statistically linked with hsCRP increase, cTnI elevation was significantly associated with AHA-ACC B₂/C type lesion, the number and the total length of stents implanted, the duration of procedure and treatment by betablockers. Multivariate analysis showed that the independent predictors of cTnI elevation were procedure duration (p = 0.032 OR = 14.2 CI 95% 7.69-100) and the absence of pretreatment with betablockers (p = 0.036, OR = 2,6 CI 95% 1.35-35).

Conclusion

cTnI elevation following PCI is very frequent and related with the duration of the procedure. Our data suggest a protective role of betablockers in the occurrence of cTnI elevation after PCI. Confirmation of the protective role of betablockers in larger cohort is mandatory.     

Association of a DNA polymorphism of the apolipoprotein AI-CIII-AIV gene cluster with myocardial infarction in a Tunisian population

Background

Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high-density lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population.

Methods

A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reaction — restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (co-dominant model odds ratio [OR]: 1.53, 95% confidence interval [CI]: 1.0-2.35, p = 0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p = 0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p = 0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls.

Conclusion

In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.     

HLA-DQB1 genotypes and islet cell autoantibodies against GAD65 and IA-2 in relation to development of diabetes post partum in women with gestational diabetes mellitus

Aims

To study HLA-DQB1 genes and islet cell autoantibodies against glutamic acid decarboxylase 65 (GADA) and insulinoma antigen-2 (IA-2A) in relation to diabetes post partum in mothers with diagnosed gestational diabetes mellitus (GDM).

Methods

During 2003-2004, women undergoing a 75 g oral glucose tolerance test (OGTT) during pregnancy were invited to participate in the Mamma Study. Cut-off level defining GDM was a 2-h capillary blood glucose of 7.8 mmol/L. 1-2 years after delivery a 75 g OGTT was performed, GADA and IA-2A were measured and HLA-DQB1 genes analysed. Data were available for 452 mothers with previous GDM and 168 randomly selected control subjects.

Results

HLA-DQB1*0602 was negatively associated with GDM (p = 0.033) and with development of diabetes post partum (p = 0.017), whereas high risk HLA were not associated with GDM or with diabetes. The presence of GADA post partum was positively associated with diabetes post partum (p = 0.0009), but not with impaired glucose tolerance.

Conclusions

Mothers with GDM and HLA-DQB1*0602 were less likely to develop diabetes after pregnancy, and type 1 diabetes associated high risk HLA genes did not predict type 1 diabetes post partum. Additionally, GADA were positively associated with diabetes development.     

Adherence to weight loss medications; post-marketing study from HMO pharmacy data of one million individuals

Introduction

Post-marketing data on weight-loss medications in free living population are a necessary adjunct to data from clinical trials.

Materials and methods

We conducted a population-based analysis of first-time medication users based on HMO pharmacy purchasing data serving > one million adults.

Results

During 5 years, usage of orlistat and sibutramine more than doubled and rates were higher during the months May-Aug. As compared to non-users (n = 1,038,828), annual weight-loss drug users (n = 7175) had higher women proportion, body-mass-index (BMI), bariatric surgery history, and usage of diabetes, depression, and cardiovascular medications (p < 0.001 for all). Among users, men had higher BMI (34.4 kg/m² vs. 32.5 kg/m²), prevalence of diabetes (25.4% vs. 10.7%) and heart disease (14.2% vs. 3.5%) than women. Mean duration of purchasing weight-loss medications was 2.1 months for orlistat and 2.9 months for sibutramine. Fewer than 2% completed 12 months of weight-loss medication therapy. Among the 25% who continued to purchase at least 4 months, BMI (sub-group analysis) reduced from 33.02 kg/m² to 32.04 kg/m² (p < 0.001). In a multivariate model, long-term adherence (≥4 months) to weight-loss medications was associated with use of sibutramine vs. orlistat (OR = 2.08; 95%CI: 1.76-2.45), and prevalence of diabetes (OR = 1.20; 95%CI: 1.01-1.25). Age, gender, and baseline BMI were not associated with long-term adherence.

Conclusions

Usage of weight-loss drugs is higher among diabetes patients. However, the poor adherence to therapy is substantially below levels reported in clinical trials.     

Association of VKORC1 −1639 G > A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus

Aims

Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 −1639 G > A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).

Methods

VKORC1 −1639 G > A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.

Results

The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p = 0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p = 0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 −1639 G > A polymorphism was an independent predictor of cIMT (p = 0.029) after adjusting for established risk factors.

Conclusions

The association between VKORC1 −1639 G > A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 −1639 G > A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.     

Association between parental history of diabetes and type 2 diabetes genetic risk scores in the PPP-Botnia and Framingham Offspring Studies

Objective

Parental history of diabetes and specific gene variants are risk factors for type 2 diabetes, but the extent to which these factors are associated is unknown.

Methods

We examined the association between parental history of diabetes and a type 2 diabetes genetic risk score (GRS) in two cohort studies from Finland (population-based PPP-Botnia study) and the US (family-based Framingham Offspring Study).

Results

Mean (95% CI) GRS increased from 16.8 (16.8-16.9) to 16.9 (16.8-17.1) to 17.1 (16.8-17.4) among PPP-Botnia participants with 0, 1, and 2 parents with diabetes, respectively (p_trend = 0.03). The trend was similar among Framingham Offspring but was not statistically significant (p = 0.07). The meta-analyzed p value for trend from the two studies was 0.005.

Conclusions

The very modest associations reported above suggest that the increased risk of diabetes in offspring of parents with diabetes is largely the result of shared environmental/lifestyle factors and/or hitherto unknown genetic factors.