Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with type 2 diabetes and its chronic complications

Subject and aims

Endothelial derived nitric oxide (eNOS) is involved in several functions playing important role in development of type 2 diabetes and insulin resistance. The aim of this study was to examine the association between eNOS intron 4 VNTR polymorphism and type 2 diabetes in an Iranian population.

Methods

A total of 220 patients with type 2 diabetes and 96 healthy control subjects were recruited from the same area. Genotyping was performed using PCR.

Results

A significant difference was found in genotype frequencies of eNOS polymorphism between patients and controls (aa + ab vs. bb p = 0.02, OR 2.0 95% CI; 1.05-3.96). Also allele a frequency was significantly increased in patients with diabetes compared with controls (p = 0.007, OR 2.1 95% CI; 1.19-4.08). We found that in patients with diabetic neuropathy the frequency of ‘a’ allele was significantly increased compared to the controls p = 0.03, OR = 1.8 95% CI (1.00-3.7). Both genotype and allele frequencies were significantly different between patients who were complication free compared to the controls [aa + ab vs. bb p = 0.007, OR = 2.6 95% CI (1.2-5.8) and p = 0.001, OR = 2.8 95% CI (1.4-5.9)] respectively with the a allele conferring the risk.

Conclusion

The association between eNOS VNTR polymorphism and T2DM seems to be stronger in patients without diabetic complications indicating diverse effect of eNOS polymorphism on diabetes and diabetic microvascular complications.     

Household cardiovascular screening of high-risk families: a school-based study.

BACKGROUND: A parental history of cardiovascular disease has a strong relationship with risk factor clusters in the offspring. This study was performed to identify major cardiovascular risk factors in middle school-aged children and their parents in both high and low-risk families. DESIGN: A school-based, cross-sectional study. METHODS: The middle schools of the 6th district of Tehran were divided randomly into two groups. A total of 169 high-risk children with their families were recruited from the first group and 105 low-risk children with their families were recruited from the second group of schools. Anthropometric and metabolic measurements were performed. RESULTS: The means of the waist circumference and waist-to-hip ratio were significantly higher in high-risk fathers. The means of total and low-density lipoprotein (LDL) cholesterol were significantly higher in both parents and children of the high-risk group. The means of the fasting plasma glucose were significantly higher in fathers and offspring of high-risk families. More fathers in high-risk families were smokers. The prevalence of increased total cholesterol, LDL-cholesterol and hyperglycemia (> or = 100 mg/dl) were higher in high-risk parents and children. The prevalence of increased body mass index (> or = 25 kg/m for parents and 85th percentile for children) was higher in fathers and children of high-risk families. CONCLUSIONS: Cardiovascular risk factors are more prevalent and clustered in high-risk families. The screening of high-risk families is essential to prevent the progression of atherosclerosis from childhood and reduce the burden of cardiovascular disease in adulthood.     

Two polymorphisms in the epithelial cell-derived neutrophil-activating peptide (ENA-78) gene

Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78) has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing. The polymorphism at position +398 (A/G from the first ATG codon) in exon 2 results in a synonymous substitution not resulting in an amino acid change. The promoter polymorphism was found at position -156 (C/G from the first ATG codon). An assay was designed for the detection of the polymorphisms using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). Allele and genotype frequencies for the promoter -156 polymorphism are presented for 107 healthy Spanish and 54 UK Caucasians. Frequencies for the exon 2 polymorphism are also presented for 63 UK Caucasians.     

Bone mineral density is related to blood pressure in men

The aim of this study was to determine the relationships between bone mineral density (BMD) and blood pressure in 214 men, age 20–76. BMD measurements were done by dual X‐ray absorptiometry using a Lunar DPXMD densitometer at the lumbar spine (L2–L4) and different femoral regions. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an MPC‐350 sphygmomanometer. Physicians gathered demographic data and participants' dietary intake of calcium were determined by using food frequency questionnaires. After adjusting for age, body mass index, dietary calcium, and exercise history, multiple linear regression models showed that DBP was negatively related to femoral neck BMD (β = ?0.145, P = 0.032) and just shy of significant association with femoral neck BMC (β = ?0.114, P = 0.079). SBP was correlated with femoral neck (r = ?0.171, P = 0.012) and Ward's (r = ?0.186, P = 0.006) BMD but not after adjusting for possible confounders. Further studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass. Am. J. Hum. Biol. 16:168–171, 2004. © 2004 Wiley‐Liss, Inc.     

Poly thymidine polymorphism and cystic fibrosis in a non-Caucasian population

Background: Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T[5], c.1210-12T[7], c.1210-12T[9] (T₅, T₇, T₉) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran. Material and methods: 40 CF patients and 40 normal individuals were screened for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients. Results: T₇ allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T₉ and T₅ represent approximately 20% and 5% of alleles respectively. T₇/ T₇ genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T₉/ T₉, T₇/ T₇ or compound heterozygote T₇/ T₉ genotypes. Conclusion: Contrary to the Caucasians, T₇ allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T₇ allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T₅, T₇, T₉ alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity.     

Use of epidemiologically well-defined subjects and existing immunofluorescence assays to calibrate a new enzyme immunoassay for human herpesvirus 8 antibodies

Agreement between assays for the detection of human herpesvirus 8 (HHV-8) antibodies has been limited. In part, this disagreement has been because assay calibration (i.e., differentiating positive from negative results) has not been done in a standardized fashion with reference to a wide spectrum of HHV-8-infected (true-positive) and HHV-8-uninfected (true-negative) persons. To describe the performance of an assay for HHV-8 antibodies more accurately, we used epidemiologically well-characterized subjects in conjunction with testing on two existing immunofluorescence assays for HHV-8 antibodies to define two groups: a group of 135 HHV-8-infected individuals (true positives), including Kaposi's sarcoma patients and those asymptomatically infected, and a group of 234 individuals with a high likelihood of being HHV-8 uninfected (true negatives). A new enzyme immunoassay (EIA), using lysed HHV-8 virion as the antigen target, was then developed. With the above true positives and true negatives as references, the sensitivity and specificity of the EIA associated with different cutoff values were determined. At the cutoff that maximized both sensitivity and specificity, sensitivity was 94% and specificity was 93%. When the EIA was used to test a separate validation group, a distribution of seropositivity that matched that predicted for the agent of Kaposi's sarcoma was observed: 55% of homosexual men were seropositive, versus 6% seropositivity in a group of children, women, and heterosexual men. It is proposed that the EIA has utility for large-scale use in a number of settings and that the calibration method described can be used for other assays, both to more accurately describe the performance of these assays and to permit more-valid interassay comparison.