Meta-analysis of MTHFR C677T polymorphism and type 2 diabetes mellitus in MENA region.

BACKGROUND AND AIMS: The association of the C677T polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) gene with susceptibility to type 2 diabetes mellitus (T2DM) has been widely debated. Therefore, our aim is to conclusively resolve this controversy in the Middle East and North Africa region population through a meta-analysis. MATERIEL AND METHODS: We identified relevant articles by searching literature databases, such as PubMed, Web of Science, and Science Direct, to retrieve studies that examined the association between the MTHFR C677T polymorphism and the risk of developing T2DM. Using meta-analysis, we calculated the odds ratio (OR) and confidence interval (CI) values of these studies to assess the susceptibility to T2DM related to the C677T polymorphism of MTHFR gene. RESULTS: In this meta-analysis, we included a total of 13 publications comprising 2072 T2DM patients and 2164 control subjects. The results of the meta-analysis suggested that there is a significant association between the C677T polymorphism and T2DM risk in overall comparisons for allele contrasts (T vs C): OR = 1.25, 95% CI = 1.04-1.50, p = 0.015 and homozygous (TT vs CC): OR = 1.44, 95% CI = 1.01-2.05, p = 0.038). Subgroup analysis revealed that the C677T polymorphism is associated with a risk of T2DM in Asian populations, while there is no significant association between this polymorphism and T2DM in Caucasian and African populations. Furthermore, there was no evidence of publication bias. CONCLUSION: Our study's results suggest that the allele contrast of the C677T polymorphism of the MTHFR gene is associated with an increased risk of T2DM in the overall population, particularly among Asians.

Association between Methylene-Tetrahydrofolate Reductase C677T Polymorphism and Human Immunodeficiency Virus Type 1 Infection in Morocco.

Human immunodeficiency virus type 1 (HIV-1) infection varies substantially among individuals. One of the factors influencing viral infection is genetic variability. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been correlated with different types of pathologies, including HIV-1. The MTHFR gene encodes the MTHFR enzyme, an essential factor in the folate metabolic pathway and in maintaining circulating folate and methionine at constant levels, thus preventing the homocysteine accumulation. Several studies have shown the role of folate on CD4+ T lymphocyte count among HIV-1 subjects. In this case-control study we aimed to determine the association between the MTHFR C677T polymorphism and HIV-1 infection susceptibility, AIDS development, and therapeutic outcome among Moroccans. The C677T polymorphism was genotyped by polymerase chain reaction followed by fragment length polymorphism digestion in 214 participants living with HIV-1 and 318 healthy controls. The results of the study revealed no statistically significant association between MTHFR C677T polymorphism and HIV-1 infection (P > .05). After dividing HIV-1 subjects according to their AIDS status, no significant difference was observed between C677T polymorphism and AIDS development (P > .05). Furthermore, regarding the treatment response outcome, as measured by HIV-1 RNA viral load and CD4+ T cell counts, no statistically significant association was found with MTHFR C677T polymorphism. We conclude that, in the genetic context of the Moroccan population, MTHFR C677T polymorphism does not affect HIV-1 infection susceptibility, AIDS development, or response to treatment. However, more studies should be done to investigate both genetic and nutritional aspects for more conclusive results.

Prevalence and risk factors of chronic complications among patients with type 2 diabetes mellitus in Morocco: a cross-sectional study.

Introduction: microvascular and macrovascular complications of type 2 diabetes mellitus (T2DM) are one of the major causes of morbidity and mortality worldwide among patients with T2DM. This study aims to estimate the prevalence of these chronic complications and identify the associated risk factors among Moroccan patients with T2DM. Methods: this cross-sectional study was conducted on 505 T2DM patients followed by the healthcare Centers of the Casablanca-Settat region from January 2017 to July 2018. The socio-demographic, anthropometric, biochemical, and clinical data were recorded using a structured survey. For statistical analysis, SPSS version 20 is used. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with chronic complications of T2DM. Results: among the 505 Moroccan patients with T2DM, 84.98% were women. The average age of the patients was 57.27±10.74 years. Diabetic eye disease was the most frequent complication (29.5%) followed by cardiovascular diseases (CVDs) (22.4%), kidney disease in diabetes (9.8%), diabetes foot (2.8%), and neuropathy (1.8%). Logistic regression analysis showed that the CVDs was associated with hypertension (OR: 2.41; 95% CI: 1.11-5.22; p=0.026), hypolipidemia treatment (OR: 2.20; 95% CI: 1.06-4.59; p=0.034), insulin use (OR= 0.39; 95%CI: 0.15-0.96, p=0.043) and LDL-C (OR: 1.01; 95% CI: 1-1.02; p=0.035) in T2DM patients. However, the major risk factors for the development of kidney disease in T2DM patients were a lack of regular physical activity (OR: 3.77; 95% CI: 1.22-11.67; p=0.021), hypolipidemia treatment (OR: 8.31; 95% CI: 1.86-36.97; p=0.005), and high serum creatinine (OR: 1.33; 95% CI: 1.16-1.53; p≤0.001). In addition, LDL-C levels were found to be a significant risk factor for diabetes eye disease (OR: 1.01; 95% CI: 1.00-1.03; p=0.008). Conclusion: this study shows that the increased duration of diabetes, insulin use, lack of regular physical exercise, hypertension, hypolipidemia treatment, high serum creatinine, and LDL-C were significant risk factors for chronic complications of T2DM in Moroccan patients.

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis.

BACKGROUND AND AIMS: The association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region). MATERIAL AND METHODS: Our data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression. RESULTS: Of 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33-2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27-3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54-3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78-6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07-2.88; p = 0.024). CONCLUSION: Our result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.

Prevalence of dyslipidemia and the relationship between HbA1C and lipid profile in Moroccan patients with T2DM: a cross-sectional study.

Introduction: the increased prevalence of dyslipidemia in patients with type 2 diabetes mellitus (T2DM) results from uncontrolled hyperglycemia and consistently contributes to an elevated risk of cardiovascular complications. This study sought to estimate the prevalence of dyslipidemia and to investigate the relationship between glycated hemoglobin (HbA1C) and serum lipid levels in Moroccan patients with T2DM. Methods: a total of 505 patients with T2DM were included in this cross-sectional study, 77.4% with chronic complications and 22.6% without. The collected data were examined using statistical package for the social sciences (SPSS) version 20.0 software and appropriate statistical methods. Results: the data analysis showed that the mean and SD of age were 57.27±10.74 years. Among 505 patients with T2DM, the prevalence of hypercholesterolemia, hypertriglyceridemia, increased low-density lipoprotein cholesterol (LDL-C), and decreased HDL-C was 41.4%, 35.9%, 27.1%, and 17%, respectively. In addition, the data analysis showed that levels of total cholesterol (TC) (p≤0.001), triglycerides (p≤0.001), Low-density lipoprotein cholesterol (LDL-C) (p≤0.001), TC/HDL-C ratio (p=0.006), and LDL-C/HDL-C ratio (p=0.006) were significantly higher in T2DM patients with complications as compared to those without complications. The patients with HbA1C > 7.0% had significantly higher values of fasting blood glucose (FBG) (p≤0.001), total cholesterol (p≤0.001), triglycerides (p≤0.001), and TC/HDL-C ratio (p=0.025) as compared to the patients with HbA1C ≤ 7.0%. The HbA1C demonstrated a significant negative correlation with age (r=-0.139), and positive correlation with FBG (r=0.673), total cholesterol (r=0.189) and triglycerides (r=0.243). Conclusion: our results showed that HbA1C is the most important biomarker of long-term glycemic control and can also be a good indicator of the lipid profile.

Methylenetetrahydrofolate Reductase Gene Polymorphisms (C677T and A1298C) and Hemorrhagic Stroke in Moroccan Patients.

BACKGROUND: The number of deaths from hemorrhagic strokes is about twice as high than the number of deaths from ischemic strokes. Genetic risk assessment could play important roles in preventive and therapeutic strategies. The present study was aimed to evaluate whether the MTHFR gene polymorphisms could increase the risk of cerebral hemorrhage in Moroccan patients. METHODS: A total of 113 patients with hemorrhagic stroke and 323 healthy controls were included in this case-control study. The C677T (rs1801133) and A1298C (rs1801131) MTHFR gene polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in all patients and controls. The genotype and allele frequencies were compared between groups using appropriate statistical analyses. RESULTS: Both groups, patients and controls, were in accordance with the Hardy-Weinberg Equilibrium. For the C677T polymorphism, the frequencies of the CC, CT, and TT genotypes were 50.44% versus 46.13%, 39.82% versus 43.03, and 9.73% versus 10.84% in controls versus patients, respectively, whereas for the A1298C polymorphism, the frequencies of the AA, AC, and CC genotypes were 56.64% versus 57.59%, 40.71% versus 37.15, and 2.65% versus 5.26% in controls versus patients, respectively. No statistically significant difference has been proved between patients and controls frequencies (P >.05) for all additive, recessive, and dominant models. Additional analyses including genotypes combination, allelic frequencies, and hemorrhagic stroke patient subtypes did not show any statistically significant difference between controls and patients/subgroup patients. CONCLUSIONS: Our findings suggested no association between MTHFR gene polymorphisms and susceptibility to hemorrhagic strokes in Moroccan patients. Further investigations should be conducted to elucidate the roles of other gene variants in the pathogenesis of this condition.

TNF A -308G>A polymorphism in Moroccan patients with type 2 diabetes mellitus: a case-control study and meta-analysis.

Type 2 diabetes mellitus (T2DM) is one of causes of mortality and morbidity in Moroccan population. The identification of genes implicated in this disease can help to found a specific treatment and to improve the quality of life for type 2 diabetic patients. In this study we analyze the association between a polymorphism (-308G>A) of TNF A promoter gene and T2DM in Moroccan patients. Five hundred and fifty-one individuals (307 patients with T2DM and 244 controls) were genotyped for this polymorphism by PCR-RFLP. This association was further reconsidered by a meta-analysis on 21 studies including 8,187 cases and 7,811 controls. We found that in Moroccan patients the -308A allele is strongly associated with T2DM (p = 0.000002; odds ratio 1.79, 95 % confidence interval 1.41-2.28). Based on our meta-analysis, there was no significant association detected between the TNF A -308G>A polymorphism and risk for T2DM. Our results suggest that the -308G>A polymorphism is a genetic risk factor for the development of T2DM in Moroccan population. On the other hand the meta analysis results led to controversial conclusions in other ethnicities.

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility.

National and ethnic mutation databases provide comprehensive information about genetic variations reported in a population or an ethnic group. In this paper, we present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data related to diseases identified in the Moroccan population. We used the PubMed, Web of Science and Google Scholar databases to identify available articles published until April 2013. The Database is designed and implemented on a three-tier model using Mysql relational database and the PHP programming language. To date, the database contains 425 mutations and 208 polymorphisms found in 301 genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow autosomal recessive mode of inheritance (74.17%) and affect endocrine, nutritional and metabolic physiology. The MGDD database provides reference information for researchers, clinicians and health professionals through a user-friendly Web interface. Its content should be useful to improve researches in human molecular genetics, disease diagnoses and design of association studies. MGDD can be publicly accessed at http://mgdd.pasteur.ma.

Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss.

BACKGROUND: Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29. AIM: We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness. MATERIALS AND METHODS: Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene. RESULTS: Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4. CONCLUSION: These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.

Analysis of CLDN14 gene in deaf Moroccan patients with non-syndromic hearing loss.

Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein has been reported to date in an autosomal recessive form of isolated hearing loss DFNB29. In order to identify the contribution of CLDN14 to inherited deafness in Moroccan population, we performed a genetic analysis of this gene in 80 Moroccan familial cases. Our results show the presence of 7 mutations: 6 being conservative and one leading to a missense mutation (C11T) which was found at heterozygous and homozygous states, with a general frequency of 6.87%. The pathogenicity of the resulting T4M substitution is under discussion. Finally, our study suggests that CLDN14 gene can be implicated in the development of hearing loss in the Moroccan population.

Clinicopathological features and molecular analysis of primary glioblastomas in Moroccan patients.

Glioblastoma is the most frequent and most aggressive primary brain tumor. Primary and secondary glioblastomas develop through different genetic pathways. The aim of this study was to determinate the genetic and clinical features of primary glioblastoma in Moroccan patients. The blood and tumor samples were obtained from a group of 34 Moroccan patients affected with primary glioblastoma. The tumors were investigated for TP53, IDH1, and IDH2 mutations using PCR sequencing analysis. Clinicopathological data showed that the mean age at diagnosis of patients was 50.06 years, the sex ratio was 11 F/23 M, and the median of Karnofsky performance score was 60. About 18 % of patients were initially treated by total tumor resection, 41 % by subtotal, and 38 % by partial resection, but biopsy was performed for a single patient (3 %). Twenty-five patients (74 %) received radiotherapy. In addition, the median survival of the all patients was 13 months following diagnosis. There was a significant impact of higher Karnofsky performance score (KPS) (≥80) on overall survival, p-log-rank test = 0.0002, whereas other parameters did not show any significant differences. The molecular analysis revealed TP53 mutations in 3/34 (8.82 %) cases; R273H, R306X, and Q136X. However, none of the analyzed samples contained the R132-IDH1 or R172-IDH2 mutations. These results showed the absence of IDH1 mutation in primary glioblastoma, confirming that this mutation is a hallmark of secondary glioblastoma. It can be used to distinguish primary from secondary glioblastomas. We found also that higher KPS was a significantly favorable factor in patients with primary glioblastoma.

c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with xeroderma pigmentosum.

Xeroderma pigmentosum is a rare autosomal recessive disease characterized by hypersensitivity to UV light which is due to alterations of the nucleotide excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the disease. Among them, the XPC gene is known to be the most mutated in Mediterranean patients. The aim of this study was to determine the frequency of the most common XPC mutation and describe the clinical features of Moroccan patients with xeroderma pigmentosum. Twenty four patients belonging to 21 unrelated Moroccan families and 58 healthy subjects were investigated. After clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25) mutation in the XPC gene was performed by PCR and automated sequencing of exon 9 in all patients and controls. The molecular analysis showed that among the 24 patients, 17 were homozygous for the c.1643_1644delTG mutation and all their tested parents were heterozygous, whereas the others (7 patients) did not carry the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21 families). None of the 58 healthy individuals carried this mutation. In addition, clinical investigation showed that the majority of the patients bearing this mutation have the same clinical features. Our results revealed that the p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum in Moroccan families. This would have an important impact on improving management of patients and their relatives.

A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

The c.242G>A mutation in LRTOMT gene is responsible for a high prevalence of deafness in the Moroccan population.

Congenital hearing impairment (HI) affects one in 1,000 newborns and has a genetic cause in 50 % of the cases. Autosomal recessive non-syndromic hearing impairment is responsible for 70-80 % of all hereditary cases of HI. Recently, it has been demonstrated that, mutations of LRTOMT are associated with profound nonsyndromic hearing impairment at the DFNB63 locus. The objective of this study is to evaluate the carrier frequency of c.242G>A mutation in LRTOMT gene and define the contribution of this gene in the etiology of deafness in Moroccan population. We screened 105 unrelated Moroccan families with non-syndromic HI and 120 control individuals for mutation in the exon 8 of the LRTOMT gene, by sequencing and PCR-RFLP. The Homozygous c.242G>A mutation was found in 8.75 % of the families tested and in 4.16 % of control in the heterozygous state. Our results show that after the GJB2 gene mutation in LRTOMT gene is the second cause of congenital hearing impairment in Moroccan patients. This finding should facilitate diagnosis of congenital deafness of the affected subjects in Morocco.

Association of spermatogenic failure with the b2/b3 partial AZFc deletion.

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3).AZFa and AZFc deletions were identified in men with severe spermatogenic failure at similar frequencies to those reported elsewhere. Gr/gr deletions were identified in case and control populations at 5.83% and 6.25% respectively suggesting that these deletions are not associated with spermatogenic failure. However, b2/b3 deletions were detected only in men with spermatogenic failure and not in the normospermic individuals. Combined with our previous data this shows an association of the b2/b3 deletion (p = 0.0318) with spermatogenic failure in some populations. We recommend screening for this deletion in men with unexplained spermatogenic failure.

Molecular analysis of the TMPRSS3 gene in Moroccan families with non-syndromic hearing loss.

Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common type of inherited hearing impairment, accounting for approximately 80% of inherited prelingual hearing impairment. Hearing loss is noted to be both phenotypically and genetically heterogeneous. Mutations in the TMPRSS3 gene, which encodes a transmembrane serine protease, are known to cause autosomal recessive non-syndromic hearing impairment DFNB8/10. In order to elucidate if the TMPRSS3 gene is responsible for ARNSHI in 80 Moroccan families with non-syndromic hearing impairment, the gene was sequenced using DNA samples from these families. Nineteen TMPRSS3 variants were found, nine are located in the exons among which six are missense and three are synonymous. The 10 remaining variations are located in non-coding regions. Missense variants analysis show that they do not have a significant pathogenic effect on protein while pathogenicity of some variant remains under discussion. Thus we show that the TMPRSS3 gene is not a major contributor to non-syndromic deafness in the Moroccan population.

Association of the MTHFR A1298C variant with unexplained severe male infertility.

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27-8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants.

Association of the C677T polymorphism in the human methylenetetrahydrofolate reductase (MTHFR) gene with the genetic predisposition for type 2 diabetes mellitus in a Moroccan population.

AIMS: Type 2 diabetes mellitus (T2DM) is a major public health problem around the world. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be associated with T2DM and its complications. This study aimed to investigate this association in the Moroccan population. METHODS: A case-control study was performed among 282 Moroccan diabetic patients and 232 healthy controls. The MTHFR C677T and A1298C polymorphisms were genotyped by polymerase chain reaction, followed by enzymatic digestion with HinfI and MboII enzymes, respectively. RESULTS: There was a significant association between C677T polymorphism and T2DM in both additive and dominant models. In addition, the 677T allele frequency differed significantly between the diabetic and control groups (26.06% vs. 33.20%, respectively). However, no significant association was found between A1298C polymorphism and T2DM. The frequencies of combined genotypes 677CC/1298AA and 677CT/1298AC differed significantly between the diabetic and control groups (32.62% vs. 20.61% and 9.57% vs. 17.55%, respectively). CONCLUSIONS: These results show an evident association between the MTHFR C677T polymorphism and T2DM in Moroccan patients but no significant association with the MTHFR A1298C polymorphism.

Maternal effect and familial aggregation in a type 2 diabetic Moroccan population.

The aim of this study is to evaluate the degree of familial aggregation of type 2 diabetes mellitus in Morocco and to investigate transmission patterns of the disease and their relationships with patients' clinical profiles. Family history of diabetes and clinical data were collected from 232 unrelated type 2 diabetic Moroccan patients. Diabetes status was recorded for first degree (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Among studied subjects, 50% reported at least one relative with diabetes and 24% had at least one parent with diabetes. Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than second degree relatives (P < 0.01). Moreover, diabetes was more frequent among mothers than fathers of probands (P = 0.02), but this maternal effect was not observed in second degree relatives. There are no significant differences in clinical and metabolic profiles between patients according to the transmission pattern of the disease. In conclusion, these results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Moroccan studied population.

Mutational analysis of the RB1 gene in Moroccan patients with retinoblastoma.

PURPOSE: Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. METHODS: After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. RESULTS: We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. CONCLUSIONS: This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families.