Significance of serum and urine neuraminidase activity and serum and urine level of sialic acid in diabetic nephropathy.

BACKGROUND: Prospective studies have reported associations among various markers of inflammation and the incidence of diabetes, and it has been proposed that inflammation has a causal role in the development of diabetes. The objective of this study was to investigate the significance of serum and urine neuraminidase activity (NA) and serum and urine sialic acid (SA) level in patients with Diabetic nephropathy. METHODS: In a prospective study, 190 diabetic patients with established diabetic nephropathy, 30 type 2 diabetes patients without any diabetic related nephropathy, and 36 non-diabetic patients with diagnosed nephropathy were enrolled. Two hundred and forty healthy individuals without diabetes or kidney disease were also enrolled as control group. Fasting venous blood samples and urine samples were collected and checked for serum and urine NA and SA level. RESULTS: In the diabetic nephropathy group, the mean value of serum and urine NA was 64.6 ± 2.6 and 11.7 ± 1.2 mU/ml, respectively, and mean values of serum and urine SA were 93.2 ± 3.6 and 17.7 ± 1.4 mg/dl, respectively. Serum and urine NA and SA levels were significantly higher in patient with diabetic nephropathy when compared to the other groups (P < 0.001). CONCLUSIONS: Our study suggests that there is a strong association between elevated serum and urine NA and serum and urine SA levels with the presence of diabetic nephropathy in type 2 diabetic patients. Further investigations are needed on the diagnostic and prognostic significance of these two inflammatory markers.

The beta-globin gene haplotypes associated with Hb D-Los Angeles [beta121(GH4)Glu --> Gln] in Western Iran.

Hb D-Los Angeles is characterized by the substitution of glutamine for glutamic acid at position 121 of the beta-globin chain. The present investigation is the first study on the beta-globin gene haplotypes associated with beta-D-Los Angeles in Western Iran. Thirty two individuals from 11 unrelated families from Western Iran were studied. The Hb D-Los Angeles status of all cases was confirmed using polymerase chain reaction (PCR) followed by digestion with EcoRl. The haplotype of the beta-globin gene cluster was determined by a PCR-RFLP (restriction fragment length polymorphism) procedure. The haplotype background of the betaA chromosomes was also determined in 35 normal subjects from the same geographic region. The beta-globin gene haplotype analysis demonstrated that all beta-D-Los Angeles genes (23 genes) were in linkage disequilibrium with haplotype I [+----++]. Among the 70 betaA chromosomes, 30 chromosomes (42.9%) were associated with haplotype I. The present study indicates the unicentric origin of the beta-D-Los Angeles gene in Western Iran. It seems that this mutation may have occurred at the same chromosomal background common in the local population.

Plasma lipids in Iranians with sickle cell disease: hypocholesterolemia in sickle cell anemia and increase of HDL-cholesterol in sickle cell trait.

BACKGROUND: The metabolism of lipids may be altered in sickle cell anemia and beta-thalassemia patients. METHODS: Plasma lipids in 24 patients with sickle cell anemia (SS), 15 patients with sickle/beta-thalassemia (ST), 19 individuals with sickle cell trait (AS) and 62 healthy individuals (AA) were measured. RESULT: Total cholesterol concentrations in both sexes with sickle cell anemia (SS males: 104.7, SS females: 142.7 mg/dl) and sickle/beta-thalassemia (ST males: 116.7, ST females: 137.5 mg/dl) were lower (P<0.05) than AS (AS males: 171.5, AS females: 185.4 mg/dl) and normal individuals (AA males: 173.7, AA females: 183.0 mg/dl). The mean HDL-cholesterol in males with SS (35.6 mg/dl) and ST (40.7 mg/dl) were (P=0.001) lower than AS males (58.9 mg/dl). However, the mean HDL-cholesterol in females with SS (43.2 mg/dl) was lower (P<0.001) than AS females (62.7 mg/dl). The mean LDL-cholesterol of males with SS (53.8 mg/dl) was lower (P<0.01) than AS (89.4 mg/dl) and control males (115.9 mg/dl). Males with ST had a lower (P<0.001) LDL-cholesterol (58.0 mg/dl) compared to control males. In females with SS the LDL-cholesterol (78.3 mg/dl) was lower (P<0.001) than control females (124.3 mg/dl). However, females with ST had lower (P<0.05) LDL-cholesterol (61.6 mg/dl) than AS (101.7 mg/dl) and control females. There was no significant difference in total concentrations of cholesterol and triglycerides between males and females with AS and those with normal hemoglobin. However, the HDL-cholesterol in both genders with AS was higher (P<0.001) than normal subjects. Also, the concentration of LDL-cholesterol in both males and females with AS was lower than control males (P<0.05) and females. CONCLUSIONS: Hemolytic stress could be associated with a significant reduction in plasma lipids and lipoproteins. It appears that patients with sickle cell anemia and individuals with sickle cell trait are at a lower risk for coronary artery disease.

Implications of the genetic epidemiology of globin haplotypes linked to the sickle cell gene in southern Iran.

To determine the origin of sickle cell mutation in different ethnic groups living in southern Iran, we studied the haplotype background of the betaS and betaA genes in subjects from the provinces of Fars, Khuzestan, Bushehr, Hormozgan, and Kerman and from the islands of Khark and Qeshm. beta-globin gene cluster haplotypes were determined using the PCR-RFLP technique. Detection of -alpha 3.7 deletion and beta-thalassemia mutations were defined by PCR and reverse dot blot techniques, respectively. The framework of the beta-globin gene was determined using denaturing gradient gel electrophoresis. We found that the betaS mutation in southern Iran is associated with multiple mutational events. Most of the patients were from two ethnic groups: Farsi speakers (presumably Persian in origin) from Fars province and patients of Arab origin from Khuzestan province. In both ethnic groups the Arab-Indian haplotype was the most prevalent. The frequencies of the Arab-Indian and African haplotypes in sickle cell anemia patients from the provinces of Fars and Khuzestan were similar. Among betaA chromosomes the Bantu A2 haplotype was the most prevalent. The decrease in alpha-globin production in SS patients and AS individuals appeared to be related to the reduction in mean cell volume and mean cell hemoglobin. The Arab-Indian haplotype gene flow into this region of Iran can be traced to the Sassanian Empire. It is likely that the influx of betaS genes linked to the Benin and Bantu haplotypes, of African origin, must have occurred during the Arab slave trade.

Polymorphism in the genes of alpha and beta tumor necrosis factors (TNF-alpha and TNF-beta) and gamma interferon (IFN-gamma) among Iranian women with breast cancer.

The association of the polymorphism in the genes of TNF-alpha, TNF-beta and IFN-gamma with breast cancer was investigated in the present study. There were no differences in the TNF-alpha and TNF-beta alleles and genotypes frequencies between breast cancer patients (n=223) and control subjects (n=267). The correlations between TNFA or TNFB alleles or genotypes and clinicopathological indices were also insignificant. However, the frequency of IFN-gamma+874 T/T genotype was significantly higher in breast cancer patients compared to those of controls (P<0.002; OR=2.03, 95% CI=1.28-3.2) which indicates that Iranian women carrying the IFN-gamma+874 T/T genotype may be exposed to an increased risk of breast cancer development.

Ile to Val polymorphism at codon 655 of HER-2 gene and breast cancer risk in Iranian women.

The earlier reports on the association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer has not been found to hold true for all ethnic populations. Two hundred and four cases and 138 controls were collected to investigate the association of HER-2 Ile655Val polymorphism with the risk of breast cancer development and progression in Iranian population. This association was not found to be significant in the present study (OR = 1.16, 95% CI: 0.67-2.03). The association between HER-2 genotypes frequency and clinicopathological data was also insignificant, suggesting that the HER-2 polymorphism at codon 655 is unlikely to be a susceptibility locus in Iranian patients with breast cancer.