**Author details**

Tekin Guney1\*, Aysun Senturk Yikilmaz2 and Imdat Dilek2

\*Address all correspondence to: tekin‐guney@hotmail.com

1 Department of Hematology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey

2 Department of Hematology, Yildirim Beyazit University Medical Faculty, Ankara, Turkey

## **References**

Another study which researched vitamin B12 prevalence among the middle‐aged and elderly

108 Epidemiology of Communicable and Non-Communicable Diseases - Attributes of Lifestyle and Nature on Humankind

Vitamin B12 deficiency resulting from drug use has been shown in several previous studies and indeed is still being discussed. Especially, metformin, which is used to treat diabetes mellitus type‐2 (DM), influences vitamin B12 absorption by affecting the calcium‐dependent ileal

However, there are studies which defend the contrary [42, 43]. Neither intestinal motility changes nor bacterial over reproduction could be shown in these studies. The relationship between vitamin B12 absorption and metformin was first observed in 30% of type‐2 diabetic patients in 1971, and Ting et al. also found a relationship between vitamin B12 and the use of

Vitamin B12 deficiency related with the use of metformin was observed among 30 patients, 90% of whom had minor hematological abnormalities, 30% had mild peripheral neuropathy, and

A meta‐analysis, which evaluated six randomized controlled trials, found that using metfor‐ min in different doses caused vitamin B12 deficiency and there was a correlation between the

Levodopa is another drug which is used for parkinsonism and believed to cause vitamin B12 deficiency. Levodopa has an effect on vitamin B12 levels by affecting the catechol‐*O*‐methyl transferase pathway and carbidopa metabolism [47‒49]. According to these studies, vitamin B12 levels should be checked before planning to use metformin and levodopa for a long‐term

The prevalence of vitamin B12 deficiency was reported to be very high over the last dec‐

Consequently, vitamin B12 deficiency has been found to be very common in specific groups of the population, and there is a high risk of vitamin B12 deficiency as far as vegetarians, infants, pregnant and breastfeeding mothers, and the elderly are concerned. There is clearly a need to establish both national and prophylaxis programs in order to prevent vitamin B12 deficiency

and Imdat Dilek2

1 Department of Hematology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara,

2 Department of Hematology, Yildirim Beyazit University Medical Faculty, Ankara, Turkey

ade that is why national programs have been established to prevent it [50, 51].

in Europe reported vitamin B12 deficiency to be between 5 and 46% [38‒40].

absorption of intrinsic factor‐vitamin B12 complex [41, 42].

two patients had symptomatic anemia and pancythopenia [45].

metformin dosage and level of vitamin B12 deficiency [46].

metformin in treatment doses in 2006 [16, 44].

period.

among such cases.

**Author details**

Turkey

Tekin Guney1\*, Aysun Senturk Yikilmaz2

\*Address all correspondence to: tekin‐guney@hotmail.com


[28] Kwok T, Cheng G, Lai WK, et al. Use of fasting urinary methylmalonic acid to screen for metabolic vitamin B12 deficiency in older persons. Nutrition. 2004;20:764‒8.

[14] Allen LH. How common is vitamin B12 deficiency? Am J Clin Nutr.

110 Epidemiology of Communicable and Non-Communicable Diseases - Attributes of Lifestyle and Nature on Humankind

[15] Stabler SP, Allen RH. Vitamin B12 deficiency as a world‐wide problem. Annu Rev Nutr.

[16] Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B12 deficiency

[17] Dhonukshe‐Rutten RA, van Dusseldorp M, Schneede J, et al. Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Eur

[18] Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow‐ up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab.

[19] Geisel J, Schorr H, Bodis M, et al. The vegetarian lifestyle and DNA methylation.

[20] Gibson RS, Abebe Y, Stabler S, et al. Zinc, gravida, infection, and iron, but not vitamin B‐12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J

[21] Gilsing AM, Crowe FL, Lloyd‐Wright Z, et al. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross‐sectional analysis of the EPIC‐Oxford cohort study. Eur J Clin Nutr. 2010;64:933‒

[22] Hermann W, Obeid R, Schorr H, et al. Functional vitamin B12 deficiency and determi‐ nation of holotranscobalamin in populations at risk. Clin Chem Lab Med. 2003;41:1478‒

[23] Hermann W, Obeid R, Schorr H, et al. Enhanced bone metabolism in vegetarians—the

[24] Hermann W, Schorr H, Purschwitz K, et al. Total homocysteine, vitamin B12, and total

[25] Hermann W, Schorr H, Obeid R, et al. Vitamin B12 status, particularly holotran‐ scobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia

[26] Hermann W, Obeid R, Schorr H, et al. The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Curr Drug Metab.

[27] Kwok T, Cheng G, Woo J, et al. Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women. Am J Hematol. 2002;70:186‒

role of vitamin B12 deficiency. Clin Chem Lab Med. 2009;47:1381‒87.

antioxidant status in vegetarians. Clin Chem. 2001;47:1094‒1101.

in vegetarians. Am J Clin Nutr. 2003;78:131‒36.

in patients receiving metformin. Arch Intern Med. 2006;166(18):1975‒79.

2009;89(Suppl):S693‒96.

J Nutr. 2005;44:341‒47.

Nutr. 2008;138;581‒86.

39.

88.

2005;6:47‒53.

90.

Clin Chem Lab Med. 2005;43:1164‒69.

2000;44:229‒34.

2004;24:299‒326.


#### **β-Thalassemia: Genotypes and Phenotypes β-Thalassemia: Genotypes and Phenotypes**

Tamer Hassan, Mohamed Badr, Usama El Safy, Mervat Hesham, Laila Sherief and Marwa Zakaria Tamer Hassan, Mohamed Badr, Usama El Safy, Mervat Hesham, Laila Sherief and Marwa Zakaria

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64644

#### **Abstract**

[42] Bauman WA, Shaw S, Jayatilleke ES, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care.

112 Epidemiology of Communicable and Non-Communicable Diseases - Attributes of Lifestyle and Nature on Humankind

[43] Scarpello JH, Hodgson E, Howlett HC. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet Med. 1998;15(8):651‒6.

[44] Tomkin GH, Hadden DR, Weaver JA, Montgomery DA. Vitamin‐B12 status of patients

[45] Andrès E, Federici L. Vitamin B12 deficiency in patients receiving metformin: clinical

[46] Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: systematic

[48] Ceravolo R, Cossu G, Bandettini di Poggio M, et al. Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study. Mov Disord. 2013;28(10):1391‒

[49] Müller T, van Laar T, Cornblath DR, Odin P, Klostermann F, Grandas FJ, Ebersbach G, Urban PP, Valldeoriola F, Antonini A. Peripheral neuropathy in Parkinson's disease: levodopa exposure and implications for duodenal delivery Parkinsonism Relat Disord.

[50] Allen LH. Folate and vitamin B12 status in the Americas. Nutr Rev. 2004;62:29‒33.

[51] McLean E, de Benoist B, Allen LH. Review of the magnitude of folate and vitamin B12

[47] Rajabally YA, Martey J. Neuropathy in Parkinson disease: prevalence and

on long‐term metformin therapy. Br Med J. 1971;19;2(5763):685‒7.

data. Arch Intern Med. 2007;167(7):729.

review. PLoS One. 2014; 24;9(6):e100379.

determinants. Neurology. 2011;77(22):1947‒50.

deficiencies worldwide. Food Nutr Bull. 2008;29:38‒51.

2000;23:1227‒31.

7.

2013;19(5):501‒7.

β-Thalassemias are extremely heterogeneous at the molecular level. More than 200 disease-causing mutations have been identified. The majority of mutations are single nucleotide substitutions. Rarely, β-thalassemia results from gross gene deletion. The degree of globin chain imbalance is determined by the nature of the mutation of the βgene. β0 refers to the complete absence of production of β-globin on the affected allele. β+ refers to alleles with some residual production of β-globin (around 10%). In β++, the reduction in β-globin production is very mild. The broad spectrum of β-thalassemia alleles can produce a wide spectrum of different β-thalassemia phenotypes. In this chapter, we review the molecular basis of the marked heterogeneity of the thalassemia syndromes or in other words the genotype-phenotype relationship in β-thalassemia.

**Keywords:** β-Thalassemia, genotype, phenotype, mutation, disease
