Role of 19 SNPs in 10 genes with type 2 diabetes in the Pakistani population.

Meta-GWAS report numerous variants associated with type 2 diabetes (T2D), however, for diabetic retinopathy (DR) no loci achieved genome-wide significance. There are limited candidate gene analyses for T2D and/or DR reported from the Pakistani population. Therefore, the current study was designed to evaluate the genetic association of 10 loci with T2D, non-proliferative DR (NPDR), and proliferative DR (PDR). In total 375 T2D cases and 205 controls were collected. The T2D cases included diabetic no retinopathy (n = 196), NPDR (n = 95), and PDR (n = 84). Genomic DNA was isolated, and 19 SNPs were genotyped. To determine association of SNPs with T2D, logistic regression analyses were performed adjusting for age and sex. Moreover, for association of SNPs with NPDR and PDR logistic regression analyses adjusting for diabetes duration and age of T2D onset were performed. In multivariate analysis, the minor alleles of rs1043618 [G > C, odds ratio (OR) 95% confidence interval (CI) = 1.45 (1.13-1.87), p = 4.00E-3], rs3807987 [G > A, 1.87 (1.22-2.94), p = 0.01], rs12672038 [G > A, 1.53 (1.04-2.30), p = 0.03] and rs2055858 [G > C, 1.70 (1.20-2.43), p = 3.00E-3] were associated with higher risk while rs1801133 (C > T, 0.59 (0.42-0.83), p = 2.28E-3) was associated with a lower risk of T2D. Moreover, minor alleles of rs2055858 [G > C, 1.77 (1.17-2.68), p = 0.02], and rs3759890 [C > G, 2.17 (1.39-3.39), p = 4.00E-3] showed an association with PDR when compared with DNR. However, only the association of rs1801133 survived multiple test correction. Hence, we report that rs1801133 is associated with T2D in the Pakistani population. In addition, out of studied 10 genes 8 proteins had higher interactions among themselves that are predicted to be partially biologically connected, as a group.

CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children.

Three index patients with hyperhomocysteinemia and ocular anomalies were screened for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR-restriction fragment length polymorphism. Sanger sequencing was performed for CBS exonic sequences along with consensus splice sites. In the case of MTHFR polymorphisms, all the patients were heterozygous CT for the single nucleotide polymorphism (SNP) C677T and were therefore carriers of the risk allele (T), while the patients were homozygous CC for the risk genotype of the SNP A1298C. CBS sequencing resulted in the identification of two novel mutations, a missense change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del; p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T; p.Thr257Met) in exon 10 of the gene was also identified. The mutations were present homozygously in the patients and were inherited from the carrier parents. This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia.

Burr Hole Evacuation of Extradural Hematoma in Mass Trauma. A Life Saving and Time Saving Procedure: Our Experience in the Earthquake of 2005.

AIM: To observe the outcome of burr hole evacuation of extradural hematoma (EDH) in mass head injury. MATERIAL AND METHODS: This study included patients of any age who sustained head injury in the earthquake of October 8, 2005, were diagnosed as EDH on computed tomography (CT) scan and were admitted in the neurosurgery ward over a period of 3 days. All patients were followed by serial CT scans and neurological assessments. RESULTS: A total of 36 patients were included in this study. There were 25 male and 11 female patients and the age range was from 5 years to 50 years. All cases were the victim of the earthquake. All patients underwent surgery for evacuation of EDH through a single burr hole. One patient required craniotomy for EDH due to neurological deterioration on the second postoperative day, and 1 patient died. CONCLUSION: As EDH is potentially fatal lesion, evacuation of EDH through a single burr hole has good outcome with less chances of recurrence and complications in mass head injured patients as seen with earthquakes.

Frequency of conservatively managed traumatic acute subdural haematoma changing into chronic subdural haematoma.

BACKGROUND: Traumatic brain injury represents a significant cause of mortality and permanent disability in the adult population. Acute subdural haematoma is one of the conditions most strongly associated with severe brain injury. Knowledge on the natural history of the illness and the outcome of patients conservatively managed may help the neurosurgeon in the decision-making process. METHODS: We prospectively analysed 27 patients with age ranges 15-90 years, in whom a CT scan diagnosis of acute subdural haematoma was made, and in whom craniotomy for evacuation was not initially performed, to the neurosurgery department of Ayub Teaching Hospital Abbottabad (2008-2011). Patients with deranged bleeding profile, anticoagulant therapy, chronic liver disease, any other associated intracranial abnormalities, such as cerebral contusions, as shown on CT, were excluded from this study. All patients were followed by serial CT scans, and a neurological assessment was done. RESULTS: There were 18 male and 9 female patients, Cerebral atrophy was present in over half of the sample. In 22 of our patients, the acute subdural haematoma resolved spontaneously, without evidence of damage to the underlying brain, as shown by CT or neurological findings. Four patients subsequently required burr hole drainage for chronic subdural haematoma. In each of these patients, haematoma thickness was greater than 10 mm. The mean delay between injury and operation in this group was 15-21 days. Among these patients 1 patient required craniotomy for haematoma removal due to neurological deterioration. CONCLUSION: Certain conscious patients with small acute subdural haematomas, without mass effect on CT, may be safely managed conservatively, but due to high risk of these acute subdural haematoma changing into chronic subdural haematoma these patients should be reinvestigated in case of neurological deterioration.