ADAMTSL2 mutations determine the phenotypic severity in geleophysic dysplasia.

Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes. We developed and characterized cellular and mouse models, to replicate the genetic profile of a patient who is compound heterozygous for 2 ADAMTSL2 variants, namely p.R61H and p.A165T. The impairment of ADAMTSL2 secretion was observed in both variants, but p.A165T exhibited a more severe impact. Mice carrying different allelic combinations revealed a spectrum of phenotypic severity, from lethality in knockout homozygotes to mild growth impairment observed in adult p.R61H homozygotes. Homozygous and hemizygous p.A165T mice survived but displayed severe respiratory and cardiac dysfunction. The respiratory dysfunction mainly affected the expiration phase, and some of these animals had microscopic post-obstructive pneumonia. Echocardiograms and MRI studies revealed a significant systolic dysfunction, accompanied by a reduction of the aortic root size. Histology verified the presence of hypertrophic cardiomyopathy with myocyte hypertrophy, chondroid metaplasia, and mild interstitial fibrosis. This study revealed a substantial correlation between the degree of impaired ADAMTSL2 secretion and the severity of the observed phenotype in GD1.

Real world results of venetoclax combined with hypomethylating agents in relapsed/refractory AML.

OBJECTIVE: Relapsed/refractory AML cases are much more resistant to chemotherapy. Venetoclax is a highly sensitive BCL-2 inhibitor. It was aimed to evaluate the effects of venetoclax therapy on real-world R/R AML survival outcomes, the effects of the cytogenetic characteristics of the patients and previous clinical applications on treatment response, and venetoclax treatment toxicity. PATIENTS AND METHODS: The study included patients who only received a venetoclax-based salvage on R/R AML patients from Turkey. The study included a total of 62 patients from 6 different centers in Turkey. Response to 2 cycles of venetoclax treatment was assessed by bone marrow blast rate. The demographic data, cytogenetic characteristics, AML type, MDS type, response rates and overall survival of the patients after venetoclax combination treatment were assessed. Median age of the patients was 65 (19-85). Mean number of prior treatments was 2.67 ±1.75. RESULTS: 13 patients (21%) had a history of allogenic stem cell transplantation. 58 (93.5%) had received HMA therapy before venetoclax. 36 patients (58.1%) had de-novo AML, and 25 (40.3%) previously had MDS. Treatment response was evaluated as complete remission (n = 21, 33.9%), partial response (n = 17, 27.4%), and treatment failure (n = 24, 38.7%). Patients in the TF group were significantly more likely to have poor cytogenetic and to have received allogeneic transplants. The mean estimated overall survival after the venetoclax treatment was 9.13 ± 0.75 months. CONCLUSIONS: The study population consisted of a group of patients who had relapsed or primary refractory disease with poor prognosis, despite numerous rounds of chemotherapy. It is our belief that the high response rates obtained with the combination of venetoclax/HMA, and having obtained positive results with poor risk patients, indicated a promising perspective for R/R AML patients.

Effect of Cytokine Genes in the Pathogenesis and on the Clinical Parameters for the Treatment of Multiple Myeloma.

In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-ß1), interferon gamma (IFN-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10), and clinical parameters and prognosis in patients with multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population for the first time except TNF-α. We analyzed five cytokine genes in 113 cases with MM and 113 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype associated with high expression in TNF-α gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-α gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-γ (+874) variant TT genotype was increased (p = 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to controls. IFN-γ (+874) T allele was higher in MM patients compared with controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR = 0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with 5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival (EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR = 2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR = 0.435, p = 0.002) with negative prognostic values. Our results suggested that TNF-α gene (-308) AG genotype and IFN-γ (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM.

Effects of TNFα, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters, Prognosis and Survival of Multiple Myeloma Cases.

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFα), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFα, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNF α(-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFαgene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNF α(-308) GG genotypes may have roles in myeloma pathogenesis.

Research on and clinical importance of duplications in various chromosomal regions in addition to Philadelphia chromosome in chronic myeloid leukemia.

PURPOSE: To investigate the chromosomal aberrations in chronic myelogenous leukemia (CML), particularly in chromosomal regions which carried 67 genes pertaining to oncogenes, transcription factors, signal transduction, tumor suppressors, apoptosis etc, in addition to Philadelphia (Ph+) chromosome by multiplex ligation-dependent probe amplification (MLPA) method and to compare them with clinical parameters. METHODS: The aberrations were investigated in 48 CML patients receiving imatinib therapy and a group of 15 healthy controls, by using the MLPA method between 2000 and 2009. The obtained results were compared both between patient and control groups and with clinical parameters. RESULTS: Duplication was detected in the fibroblast growth factor receptor 1 (FGFR1) gene of 2 patients, inosine 5' monophosphate dehydrogenase 1 (IMPDH1) gene of 4, postmeiotic segregation increased S. Cerevisiae 2 (PMS2) gene of 1, nuclear factor kappa beta (NFKB) of 5 and T-cell translocation 2 (LMO2) gene of 1 patient. Univariate analysis showed that splenomegaly, advanced age, Sokal risk score (SRS) and the duplications in IMPDH1 and FGFR1 genes significantly shortened 7-year event-free survival (EFS); multivariate analysis showed that only the duplications in IMPDH1 and FGFR1 genes were the factors that significantly affected EFS. No statistically significant correlations were detected between duplications and other clinical parameters. CONCLUSION: Duplications in 4 genes (FGFR1, IMPDH1, PMS2, LMO2) in addition to Ph+ chromosome in CML patients were detected for the first time. This study indicates that chromosomes 7 and 8 should be particularly investigated in more detail in addition to the Ph+ chromosome for better determination of disease prognosis and selection of alternative treatments.

Management of Chenopodium polyspermum toxicity with plasma exchange and hemodialysis.

A 45-year-old male patient was admitted to our emergency department complaining of fatigue, headache, mild confusion, nausea, and vomiting. He had had Type 2 diabetes mellitus for 10 years that was managed with insulin injections. Two days before the onset of symptoms, he had consumed the natural herb Chenopodium polyspermum to regulate his blood glucose levels. Upon examination, he was found to be experiencing tenderness in the upper left abdominal area, icteric sclera, and pallor conjunctivas. Laboratory tests revealed that he was anemic and had increased levels of indirect bilirubin, lactic dehydrogenase, and creatinine in blood. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The best supportive care was provided, and therapeutic plasma exchange (TPE) treatments were administered. TPE was performed five times and hemolytic findings improved. The patient then developed chronic renal failure and was transferred to the dialysis program and discharged. In this article, we present a case with hemolytic and renal toxicity induced by the ingestion of Chenopodium polyspermum that was managed with TPE and hemodialysis.

DNA repair genes polymorphisms in multiple myeloma: no association with XRCC1 (Arg399Gln) polymorphism, but the XRCC4 (VNTR in intron 3 and G-1394T) and XPD (Lys751Gln) polymorphisms is associated with the disease in Turkish patients.

OBJECTIVE: This study aims to investigate the association between the polymorphisms in DNA repair genes (XPD, XRCC1, and XRCC4) and clinical parameters in patients with multiple myeloma (MM), their effects on prognosis and their roles in susceptibility to MM. PATIENTS AND METHODS: Sixty patients, diagnosed with MM and 70 individuals as the healthy control group were included in the study. Gene polymorphisms were detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism method. When the genotype frequencies of XPD (Llys751Gln) and XRCC1 (Arg399Gln) genes were examined in the patient and control groups, no significant difference was detected, while a significant association was found in XRCC4 (VNTR in intron 3 and G-1394T) polymorphisms. A significant association was found in the MM patients group for AA genotype and event-free survival (EFS) in terms of XPD (751) gene polymorphism (P = 0.047). When VNTR intron 3 polymorphism was compared for genotype frequency, DD genotype was found to be significantly low (P = 0.012) in the patient group, whereas GG and TT genotypes were found to be significantly lower in the patient group for the genotype frequency XRCC4 (G-1394T) polymorphism when compared to the control group (P = 0.015, P = 0.010, respectively). RESULTS: These data provide support for the hypothesis that a common variation in the genes encoding XRCC4 DNA repair proteins may contribute to susceptibility to myeloma. These findings require further validation in independent populations.

Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies developing against thrombocyte membrane glycoproteins (GPs), such as GPIIa/IIIa and GPIb/IX. Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were investigated in 71 patients with chronic ITP and 71 healthy controls, and they were compared with the clinical parameters. The polymorphisms in the SNPs were investigated with the polymerase chain reaction, polymerase chain reaction with sequence specific primer, and polymerase chain reaction-restriction fragment length polymorphism methods. It was found that the high expression of TNF-alpha (-308) AG phenotype significantly increased in cases with ITP (odds ratio, OR: 0.318, 95% confidence intervals, CI: 0.103-0.987, p < 0.05). TT genotype in TGF-beta 1 (codon 10) significantly decreased in ITP in comparison with the controls (OR: 0.342, 95% CI: 0.149-0.787, p = 0.016). IFN-gamma (+874) TT genotype was detected to be high in cases with ITP (OR: 3.301, 95% CI: 1.400-7.784, p < 0.05), whereas AA genotype was found to be significantly lower (OR: 4.993, 95% CI: 1.586-15.721, p < 0.05). MBL (codon 54) BB genotype (OR: 1.164, 95% CI: 1.059-1.279, p < 0.05) and IL1A A1/A2 genotype (OR: 0.249, 95% CI: 0.076-0.815, p < 0.05) were found to be significantly higher in cases with ITP than in healthy controls. TNF-alpha (-308) AG phenotype was detected to be significantly higher in steroid-refractory and splenectomized cases at the end of the first year than in the steroid-responsive (complete response (CR) and remission (R)) cases (OR: 4.137, 95% CI: 1.156-14.807, p < 0.05). When we compared the cases, from whom we obtained a CR at their first steroid response, with 12 cases, who entered R but from whom we could not obtain any CR, the frequencies of IFN-gamma (+874) AA genotype were found as 12 (20.3%) and 6 (50%) (OR: 0.082, 95% CI: 0.009-0.793, p < 0.05). MBL (codon 54) AB genotype was detected to be significantly higher in CR patients than in R cases (OR: 1.273, 95% CI: 1.110-1.459, p < 0.05). With these findings, it was found that TNF-alpha/AG, TGF-beta 1/TT, IFN-gamma/TT, MBL/BB, and IL-1RA A1/A2 genotypes were detected as the genes of susceptibility to ITP, while TNF-alpha/AG, IFN-gamma/AA, and MBL/AB genotypes might be important in response to steroid treatment.

Red cell indices and functions differentiating patients with the beta-thalassaemia trait from those with iron deficiency anaemia.

This study examined the diagnostic accuracy of nine indices to discriminate between patients with mild-to-moderate (haemoglobin 8.5 - 11 g/dl) or moderate-to-severe (haemoglobin < 8.5 g/dl) iron deficiency anaemia (IDA) from those with beta-thalassaemia (beta-TT) (n = 100 per group). Indices examined were red blood cell (RBC) count, RBC distribution width (RDW), Mentzer index (MI), Shine and Lal index (S&L), England and Fraser index (E&F), Srivastava index (S), Green and King index (G&K), RDW index (RDWI), and Ricerca index (R). Index sensitivity, specificity, and positive and negative prognostic values were examined. Youden's indices were calculated and showed: S&L > G&K > E&F > RBC = RDWI > MI > S > R > RDW to differentiate between beta-TT and mild-to-moderate IDA; and S&L > G&K > E&F = RDWI > RBC > R > MI > S > RDW to differentiate between beta-TT or moderate-to-severe IDA. For both groups, S&L and G&K offered the best discrimination and RDW the worst. S&L showed the highest Youden index for beta-TT and IDA discrimination, but sensitivity and specificity were not 100%. In both mild and severe IDA, the S&L index may be used to differentiate cases of beta-TT from IDA cases, but large clinical trials are needed to explore this further.

Serum leptin level in acute myeloid leukemia patients.

Leptin is a regulator of fat metabolism that is synthesized in adipocytes and released into circulation. The serum levels of leptin are, therefore, correlated with body fat mass and show a wide variation in healthy individuals. Leptin may have an additional indirect effect on leukemic hematopoesis. We investigated serum leptin levels with enzyme-linked immunosorbent assays in 14 acute myeloblastic leukemia (AML) patients before and after chemotherapy and compared the results with that of the levels determined 14 healthy controls. We found no significant difference between leptin levels before and after chemotherapy and control group. Therefore, serum leptin level should not be used as a diagnostic marker in acute leukemia patients. However, the possibility of regional leptin production by leukemia blasts in bone marrow stroma creates a high local concentration of leptin within bone marrow microenvironment and systemic leptin level in combination with local leptin production may affect leukemic hematopoesis.

Brucellosis-induced immune thrombocytopenia mimicking ITP: a report of seven cases.

Brucellosis continues to be an important cause of fever in underdeveloped countries and in rural areas of developed world. It is a multisystemic disease, associated with wide variety of symptoms. A wide variety of symptoms, including haematological abnormalities, such as anaemia, thrombocytopenia, pancytopenia, dissemine intravascular coagulation and leucopoenia could be seen, all of which are more common than usually thought. In this short study, we present a relatively uncommon haematological manifestation that of isolated thrombocytopenia mimicking idiopathic thrombocytopenic purpura, which we observed in seven of 114 patients who were diagnosed with brucellosis in our hospital over a 2-year period. Having given brucellosis treatment with rifampicin and doxycycline, complete remission was achieved and thrombocyte count returned to normal in all cases.

A case report of POEMS syndrome developing during the clinical course of immune thrombocytopenic purpura.

Immune thrombocytopenia is commonly seen in patients with lymphoproliferative disorders, but is rare in patients with multiple myeloma. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is defined by the presence of a peripheral neuropathy, a monoclonal plasma cell disorder, and at least one of the following: endocrinopathy, skin changes, osteosclerotic myeloma, Castleman's disease, organomegaly, edema, or papilledema. In this paper, we present a patient with immune thrombocytopenic purpura (ITP) who developed POEMS syndrome during the clinical course of his ITP, and report on the early appearance of an isolated paraneoplastic symptom before the other diagnostic components of POEMS syndrome had developed. To our knowledge, this is the first description of coexistent ITP and POEMS syndrome in the literature.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) mimicking systemic lupus erythematosus: a review of two cases.

Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited lymphadenitis commonly found in young women. It often shares clinical features with systemic lupus erythematosus (SLE), such as arthralgias, fever and leukopenia. The etiology of KFD remains unknown and controversial. Clinical course is favorable, with spontaneous remission in less than four months in almost all cases. Herein, we present two cases. The former is a 53-year old woman presenting with cervical lymphadenopathy, arthralgia, pancytopenia and positive antinuclear antibody (ANA). Lymph node biopsy revealed histopathological features compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The latter patient was a 20-year old woman presenting with left cervical lympadenopathy, a butterfly rash that was reminiscent of SLE, and a positive antinuclear antibody. Based upon clinical, histological and laboratory findings, the diagnosis of SLE was excluded. Careful attention should be paid to differentiating between KFD and SLE, because of their similar presentations, yet different clinical courses and therapeutic requirements.

Frequency of silent myocardial ischemia in type 2 diabetic patients and the relation with poor glycemic control.

The aim of the study was to investigate the frequency of silent myocardial ischemia in type 2 diabetic patients without any clinical or laboratory findings of myocardial ischemia and to examine the related factors for silent myocardial ischemia. A total of 116 type 2 diabetic patients (82 women) with a disease duration of 5-20 years were included in the study. All patients underwent stress and resting myocardial perfusion single-photon emission computed tomographic (SPECT) study with (99m)Tc-MIBI. Coronary angiography was performed in patients with ischemia established at myocardial perfusion SPECT. Ischemia was determined in 18 (15.5%) patients by myocardial perfusion SPECT. Coronary angiography performed in 17 of these patients confirmed coronary stenosis >50% in 11 patients. Thus, the prevalence of silent myocardial ischemia was 9.6%. Significant relations were found between silent myocardial ischemia and male sex, high HbA(1C) level and retinopathy. Type 2 diabetic patients (especially men) with poorly controlled diabetes mellitus or retinopathy should be screened for silent myocardial ischemia.

Bernard-Soulier syndrome in a Turkish family.

This report describes the first Turkish family to be diagnosed with Bernard-Soulier syndrome. The family consists of nine members (two parents, three sons and four daughters). The parents were first cousins. The index case, a 22 year-old-man, had a history of haemorrhagic diathesis with thrombocytopenia, giant platelets in the peripheral blood smear and a prolonged bleeding time. Refractory idiopathic thrombocytopenic purpura had been diagnosed elsewhere and a splenectomy had been performed six months previously. Ristocetin agglutination of platelets was defective and flow cytometry analysis of platelet membrane glycoprotein showed markedly reduced expression of glycoprotein lb (2.1%). Bernard-Soulier syndrome was diagnosed. Increased mean platelet volume was found in both parents, one son and three daughters. The other son and daughter were normal.

Angiotensin converting enzyme gene polymorphism and glomerular filtration rate changes in type 2 diabetic patients.

It has been suggested that an insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene may be associated with diabetic nephropathy The aim of this study was to investigate whether an association exists between ACE I/D polymorphism and glomerular filtration rate (GFR) in type 2 diabetes mellitus. A total of 128 type 2 diabetic patients were included in the study with the following ACE genotype distribution: DD 40, ID 58,11 30. I/D polymorphism was determined by polymerase chain reaction (PCR). Mean GFR was not statistically different according to ACE genotype (DD: 89.9 +/- 28.1 ml/min, ID: 99.5 +/- 25.1 ml/min, II: 96.6 +/- 19.6 ml/min). There was no significant difference in genotype distribution in normo-, micro- and macroalbuminuric patients (DD:ID:II [%], normo- 35:46:19, micro-28:55:17, macro- 31:55:14). ACE I/D polymorphism does not seem to be associated with GFR in type 2 diabetic patients.

Increased frequency of HCV but not HBV infection in type 2 diabetic patients in Turkey.

The aim of this study was to investigate the prevalence of hepatitis B and hepatitis C virus infections in type 2 diabetic patients in Gaziantep, Turkey. Six hundred and ninety-two type 2 diabetic patients and 1014 healthy blood donors were included in the study. No significant difference was found between type 2 diabetic patients and the control group for seropositivity of HBsAg (5.3% vs 5.1%, p>0.05). In contrast, anti-HCV was significantly more frequent in type 2 diabetic patients (7.5% vs 0.1%, p>0.0001). We found no significant difference for HBsAg seropositivity between type 2 diabetic patients with a disease duration of 12 months or less, but anti-HCV seropositivity was significantly more frequent in diabetic patients with a longer disease duration (p<0.05). We suggest that HCV infection is not a trigger factor for type 2 diabetes mellitus but is frequently associated with it.

Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients.

The aim of this study was to investigate whether an association exists between the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients. A total of 239 type 2 diabetic patients and 138 sex and age matched control subjects were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). Nephropathy status was determined according to urinary albumin/creatinine ratio (microg/mg) (<30 normoalbuminuria, 30-300 microalbuminuria, >300 macroalbuminuria) and retinopathy was evaluated by fundoscopic examination and by flourescein fundus angiography. The distribution of ACE I/D polymorphism and allele frequencies in diabetic patients were not significantly different from controls, DD genotype 32.2 versus 37.2%; ID genotype 50.6 versus 47.1%; and II 17.2 versus 15.2%; D allele 57.5 versus 61.2%; I allele 42.5 versus 38.8%. Genotype distribution between normo-, micro- and macroalbuminuric patients did not differ significantly (DD:ID:II (%), normoalbuminuria, 35:46:19; microalbuminuria, 28:55:17; macroalbuminuria, 31:55:14). There was also no difference in genotype distribution between patients with and without retinopathy (DD:ID:II (%), retinopathy positive, 32:51:17; retinopathy negative, 33:49:18). In conclusion, the ACE I/D polymorphism does not seem to be associated with diabetic nephropathy and retinopathy in Turkish type 2 diabetic patients.

Association between polymorphism of the angiotensin I converting enzyme gene and hypertension in Turkish type II diabetic patients.

It has been suggested that an insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene may be associated with essential hypertension. The aim of this study was to examine the association between ACE I/D polymorphism with blood pressure level and hypertension status in Turkish type 2' diabetic subjects. Hundred and seven hypertensive (78 female, 29 male) and 132 normotensive type 2 diabetic subjects (73 female, 59 male) and 138 sex and age matched control subjects (87 female, 51 male) without diabetes and hypertension were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). There were no statistically difference in genotypic and allelic frequencies of the ACE I/D polymorphism between the hypertensive and normotensive diabetic patients and control subjects. Also no significant differences was detected in systolic and diastolic blood pressure among three different genotypes. ACE I/D polymorphism does not seem to play an important role in the development of hypertension in Turkish type 2 diabetic subjects, but prospective studies may show an association between ACE gene polymorphism and the development of hypertension in diabetic subjects.