The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population

Background  

The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan.     

Optic disc haemorrhages and vascular abnormalities in a glaucoma population

Purpose: To retrospectively examine the optic disc photographs of a glaucoma population for optic disc haemorrhages, vascular occlusions and vascular abnormalities. Methods: The optic disc photographs of 906 eyes of glaucoma and suspect glaucoma patients were examined. Optic disc photographs were taken annually, where possible, with the follow-up period varying between 1 and 14 years duration (mean, 2.89). Glaucoma patients are regularly reviewed every 4–6 months and glaucoma suspects every 1–2 years, depending on the ophthalmologist. Low-tension glaucoma patients were reviewed more frequently (mean, every 2.6 months). The results of the findings were compared to a control group of 39 subjects with a mean follow-up period of 7 years, using Fisher's exact test. Results: It was found that during the period under review, 7.4% (n= 67) of eyes had optic disc haemorrhages. The highest frequency of optic disc haemorrhages (37.5%) was found in the low tension glaucoma group (P= 0.0001) followed by 11.4% of primary open-angle glaucoma eyes (P= 0.03). In the normal group there were three eyes with optic disc haemorrhages and one with a disc collateral, which constitutes 5.1% vascular changes in this sub-group. Of the study eyes 2.8% had central retinal vein occlusions, 1.3% branch vein occlusion, 1.2% disc vessel abnormalities (loops) and 1.1% disc collaterals. Discrete nerve fibre layer haemorrhages and microaneurysms were found in 0.8% and 1.8% of eyes, respectively. Conclusions: A total of 16.8% of the eyes observed in this study had either disc haemorrhages or vascular changes. The underlying trend of vascular and haemorrhagic changes in glaucoma are demonstrated in this sample, which is in general agreement with previous studies. The high percentage of optic disc haemorrhages in low tension glaucoma is highlighted. The presence of microaneurysms and nerve fibre layer haemorrhages is interesting but of unknown significance.     

Association of pupillary parasympathetic hyperreflexia and systemic inflammation in patients with systemic lupus erythematosus

In chronic inflammatory diseases, cytokines stimulate the hypothalamus pituitary adrenal axis and the hypothalamus autonomic nervous system (HANS) axis. The present study was performed to find autonomic nervous function parameters in patients with systemic lupus erythematosus (SLE) which are suitable to demonstrate the activation of the HANS axis during systemic inflammation. Thirty-four patients with SLE (age 35.3 +/- 1.9 yr) were investigated by seven standardized autonomic nervous function tests. The SLEDAI and laboratory parameters of systemic inflammation were assessed by standard techniques. Pupillary latency time hyperreflexia was found in 29.4%, whereas maximal pupillary area was hyperresponsive in only 2.9%. A total of 12% had overall cardiovascular autonomic nervous hyperreflexia. Patients with latency time hyperreflexia had more severe systemic inflammation [erythrocyte sedimentation rate (ESR): P < 0.001; C-reactive protein (CRP): P = 0.0094; fibrinogen: P < 0.001; albumin: P = 0.003; antinuclear antibodies: P = 0.020]. The longitudinal study of 13 patients during 4 yr demonstrated a parallel increase and decrease in latency time percentile and ESR. SLE patients with increased systemic inflammation had an activated HANS axis which can be measured by a parasympathetic pupillary reflex test.      

Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.