Tehran University Medical Journal

---

Background: The Fontan operation is the definitive operation for palliation of complex congenital heart disease with single –ventricle physiology. The use of the extra cardiac conduit has recently been gaining popularity. The purpose of this study was to compare the outcomes of extra cardiac conduit Fontan procedure (off-pump technique) and that of traditional technique (lateral tunnel technique) in which cardiopulmonary bypass is routinely used.
Methods: Forty one patients in different age groups underwent extra cardiac conduit Fontan procedure between April 2001 and December 2004. Data were collected from ICU sheets, files and during follow up visits. Under general anesthesia and through median sternotomy, using two temporary decompressing shunts, superior vena cava implanted on right pulmonary artery and a conduit interposed between transected inferior vena cava and main pulmonary artery. Fenestration was done in almost all patients and previous shunts were closed if there were any.
Results: Of our patients, 13 were female and 28 were male. Mean age of the patients was 11.1 years (SD=7.8).In 24.4% of cases Fontan procedure was done as the first palliative surgery and in 75.6% of them there was previous history of palliative procedures. In 6 patients (14.6%) we were constrained to use cardiopulmonary bypass which was predictable or necessary in 50% of cases. There was no reoperation due to post operative bleeding. Two cases suffered from prolonged plural effusion. Our in-hospital mortality was 9.8%. During 2-24 months follow up, we found two cases who were in NYHA functional class II and one case in functional class I.
Conclusion: Extra cardiac conduit Fontan procedure could be used in a safe way. The results of this study were comparable and even in some cases better than that of the traditional technique.

---

Background: Uterine leiomyoma is one of the most common benign smooth muscle tumors occurring in 20-40% of women worldwide in their reproductive years. Recent studies revealed that estrogen plays an important role in the pathogenesis of this disease. Since glutathione S-transferase (GST) gene family are involved in the biosynthesis of estrogen, the prior probability that variants at this locus are associated with uterine leiomyoma is likely to be above the null. Therefore, this study was carried out to examine whether GSTP1 polymorphism (Ile105Val) is associated with increased risk of uterine leiomyoma in Iranian population. Methods: In this case-control study, 50 women diagnosed with uterine leiomyoma and 50 healthy controls were recruited from subjects referred to the Pasteur Institute of Iran from November 2012 to September 2013. The genomic DNA was extracted from peripheral blood leucocytes using the standard phenol-chloroform method and subsequently the GSTP1 polymorphism was genotyped using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Logistic regression analysis was applied to estimate odds ratios and 95% confidence intervals after age adjustment using the SPSS statistical software package, version 18.0. Results: The results showed significant differences between case and control groups in terms of genotype frequency (P<0.0001). In addition, the results indicated that the presence of the valine allele significantly increased risk of uterine leiomyoma about three times more in individuals carrying the mutant allele compared to control group (Odds Ratio: 3.34 95%CI: 1.82-6.15 P<0.0001). Conclusion: To our knowledge, this is the first study performed in Iranian population assessing the association between GSTP1 Ile105Val polymorphism and risk of uterine leiomyoma. However, further extensive studies with a large number of samples from different populations and ethnicities are required to validate the results obtained in this study.

---

Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gap-polymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10 P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease.

---

Background: The major issue to address in endometriosis etiology is to identify the genetic changes in the disease and their occurrence in different populations. Uncovering these genetic changes may be important in developing potential biomarkers for early diagnosis and prognosis of endometriosis. Among all endometriosis susceptibility genes studied before, convincing association has been found with variants in the estrogen receptor alpha (ESR1) gene and this disease however, the contributions of these genetic variants in different populations and ethnic groups are not similar. Accordingly, this study was carried out to replicate the previous findings to assess whether this polymorphism is associated with endometriosis in Iranian women. Methods: A case-control study was designed to determine the possible association between ESR1-351A>G variant and occurrence of endometriosis. The study group consisted of 100 subjects diagnosed with endometriosis as case group and 100 fertile women without endometriosis as controls recruited from subjects referred to the Tehran Women’s General Hospital between January to September 2013. All subjects were genotyped for this marker using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR). Association of risk allele (G) with endometriosis was as-sessed using PLINK software after age adjustment. Results: The results showed that the genotype frequencies were in Hardy-Weinberg Equilibrium (HWE) in both case (F=0.04, P:0.67) and control (F=0.02, P:0.83) groups. In addition, there were no significant differences between case and control groups in terms of genotype frequencies (P=0.17). Moreover, the results indicated that the presence of risk allele (G) did not significantly increase risk of endometriosis (OR: 1.43, 95%CI: 0.96-2.13, P=0.07). Conclusion: The results do not support the previous findings of an association between -351A>G genetic polymorphism in ESR1 gene and endometriosis. Therefore, comprehensive genetic approaches including linkage analyses and family-based tests, together with a number of replication studies with large sample size, are needed to make conclusive claims about the role of this genetic polymorphism in susceptibility to endometriosis.

---

Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146 however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10^-2) to strong association in European descent populations (P= 2.0×10^-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10^-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10^-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10^-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.

---