Consanguinity decreases risk of breast cancer – cervical cancer unaffected

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40–65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 – 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 – 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 – 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected. © 2001 Cancer Research Campaign http://www.bjcancer.co

Consanguinity and reproductive health among Arabs

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

Implication of genetic variants in overweight and obesity susceptibility among the young Arab population of the United Arab Emirates

© 2020 Elsevier B.V. Objective: Overweight and obesity are major risk factors for Type 2 Diabetes Mellitus (T2DM), cardiovascular disease (CVD) and cancer. Genetic predisposition has been shown to play a key role in obesity, and genome-wide association studies (GWAS) have identified multiple loci linked with obesity in various ethnic groups. The aim of this study was to validate the reported genetic variants associated with obesity and overweight in a young UAE Arab population. Methods: Twenty-two associated single nucleotide polymorphisms (SNPs) at 11 loci (FTO, MC4R, TMEM18, KCTD15, MTCH2, SH2B1, TFAP2B, GNPDA2, NEGR1, PCSK1 and BDNF) were studied in 392 controls and 318 overweight/obese young Emiratis (aged 18–35 years). Results: After adjusting for age and smoking, rs3751812 of the FTO gene was associated with overweight/obesity in male participants (p-value \u3c 0.016), while SNPs rs17782313, rs571312 of the MC4R gene and rs12463617 of the TMEM18 gene were significantly associated with overweight/obesity in female participants (p-value = 0.001, 0.028, 0.044, respectively). Follow-up association tests and logistic regression revealed the contribution of the FTO rs3751812 and MC4R rs571213 SNPs to the risk of overweight/obesity after adjusting for age, sex and smoking (p-value = 0.044, 0.049, respectively). In addition, the FTO rs3751812 was associated with the risk of overweight/obesity after adjusting for the effect of other markers (rs17782313, rs571312, rs2867125, rs6548238 and rs12463617) (p-value = 0.035). A significant gene-gene interaction was seen between FTO, MCR4 and TMEM18 (p-value = 0.013). Conclusions: Our data demonstrates that rs3751812 of the FTO gene is the key SNP associated with risk of overweight/obesity among the young UAE Arab population, in alignment with previous findings. Our results also indicate that the identified genes stratify with sex and risk of overweight/obesity. In addition to their direct association with overweight/obesity, rs17782313 and rs571312, as well as rs2867125 and rs6548238, may have a modifying effect on the risk of overweight/obesity caused by the rs3751812. Population-specific, sex-specific genetic profiling is important in understanding the heritability of obesity

Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population

Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation

Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?

<p>Abstract</p> <p>Background</p> <p>The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α⁺-thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria.</p> <p>Methods</p> <p>In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different α⁺-thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria.</p> <p>Results</p> <p>Inbreeding increases the frequency of α⁺-thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced α⁺-thalassemia frequency) mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals). When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population.</p> <p>Conclusion</p> <p>Consanguineous marriages may increase the overall fitness of populations with endemic malaria.</p

Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects

This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its “direct” derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects

Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disease, characterized by neonatal/early-onset non-autoimmune insulin-requiring diabetes associated with skeletal dysplasia and growth retardation. Fewer than 60 cases have been described in the literature, although WRS is now recognised as the most frequent cause of neonatal/early-onset diabetes in patients with consanguineous parents. Typically, diabetes occurs before six months of age, and skeletal dysplasia is diagnosed within the first year or two of life. Other manifestations vary between patients in their nature and severity and include frequent episodes of acute liver failure, renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Bone fractures may be frequent. WRS is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3), also known as PKR-like endoplasmic reticulum kinase (PERK). PERK is an endoplasmic reticulum (ER) transmembrane protein, which plays a key role in translation control during the unfolded protein response. ER dysfunction is central to the disease processes. The disease variability appears to be independent of the nature of the EIF2AK3 mutations, with the possible exception of an older age at onset; other factors may include other genes, exposure to environmental factors and disease management. WRS should be suspected in any infant who presents with permanent neonatal diabetes associated with skeletal dysplasia and/or episodes of acute liver failure. Molecular genetic testing confirms the diagnosis. Early diagnosis is recommended, in order to ensure rapid intervention for episodes of hepatic failure, which is the most life threatening complication. WRS should be differentiated from other forms of neonatal/early-onset insulin-dependent diabetes based on clinical presentation and genetic testing. Genetic counselling and antenatal diagnosis is recommended for parents of a WRS patient with confirmed EIF2AK3 mutation. Close therapeutic monitoring of diabetes and treatment with an insulin pump are recommended because of the risk of acute episodes of hypoglycaemia and ketoacidosis. Interventions under general anaesthesia increase the risk of acute aggravation, because of the toxicity of anaesthetics, and should be avoided. Prognosis is poor and most patients die at a young age. Intervention strategies targeting ER dysfunction provide hope for future therapy and prevention