INTRODUCTION:

Mitochondria as cell organelle present in cytoplasm and functions are to produce ATP in aerobic conditions by means of oxidative phosphorylation. This progression is intervening by the multiprotein enzyme complexes I–V in respiratory electron transport chain (ETC) and with the help of two electron carriers, cytochrome c and coenzyme Q (CoQ). A major contribution to which mitochondria make are the cellular processes - apoptosis (instructed cell death), together with other specific functions as per cell-type. The Electron Transport Chain of mitochondria is efficient in ATP production and is a major outcome of whole body energy balance and heat production. Furthermore, mitochondria are the prevalent basis for producing reactive oxygen species (ROS).

The degree of manufacture also associates to the union of ATP manufacture to consumption of oxygen. In elegance of the essentiality of oxidative phosphorylation for the normal functioning and activity of nearly all cells, it is not astounding that dysfunction of mitochondria can influence practically any organ system. The incorporated function of approximated 1500 gene products is obligatory for normal biogenesis, function and integrity of mitochondria. Moreover, the mitochondria possess genome, having numerous as a circular, and double-strand DNA molecule consisting of a 16,569-nucleotide sequence. Sequence of mtDNA holds 37 genes out of which 13 genes encoded mitochondrial protein mechanisms of the electron transport chain (ETC). Rest of the 22 tRNA- and 2 rRNA-encoding genes are devoted to the course of decoding the 13 mtDNA-encoded proteins. Mitochondrial disease originates from mutations in the nuclear genome which are as follows: i) nuclear genomic mutations- disrupts the integrity of the mitochondrial genome itself, (ii) mutations in nuclear genes that encode structural components causes disorders, and (iii) mutations in nuclear genes that encode proteins indirectly related to oxidative phosphorylation causes mitochondrial disorders.

The highly polymorphic mtDNA inheritance is entirely through the maternal side. Populations of world can be classified into numerous mtDNA haplogroups occurred because of definite SNPs spread all over the genome of mitochondria, suggesting mutations gathered by a separate maternal lineage (Samuels, 2006).

Mitochondrial DNA Haplogroups in Various Diseases:

The mitochondrial DNA has the elementary role in cellular metabolism. Association between mtDNA lineages and multifactorial diseases and aging, have been investigated by number of studies (De Benedictis et al. 1999; Ruiz-Pesini et al. 2000; Carrieri et al. 2001; Niemi et al. 2003; Mancuso et al. 2004; van der Walt et al. 2004).Human populations are divided into haplogroups M, N, U, R, HV, D,E, G,Q, P, J, T,K, B,F O,A,S. Frequency of these haplogroups varies geographically and ethnically. Haplogroup frequencies geographical variations help in consistent finding of restrained haplogroup associations with common and uncommon disorders.

a) Mitochondrial DNA and Neurodegeneration:

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most incident and prevalent in the population ages and are increasing. Oxidative stress and mitochondrial dysfunction have been associated with both these disorders and has been anticipated that mitochondrial genome mutations have a vital role in neurodegeneration in Alzheimer's disease (AD) and Parkinson's disease (PD) patients (Howell, 2005).

Alzheimer's disease:

Chagnon and co-workers (1999) described that Haplogroup T is not highly characterized in Alzheimer Diseased patients, although haplogroup J were the most-represented haplogroup in them. Carrieri et al. (2001) reported his finding on sample of Italian subjects that in AD patients who were apolipoprotein (Apo) E4 carriers K and U haplogroups were present at a lower frequency than in non-carriers. This suggests that major AD risk factor might be neutralised by K and U -- the E4 allele carriers.

Van der Walt (2004) reported (independently from ApoE genotype) that males designated in haplogroup U had a considerable higher probability of Alzheimer Disease, while in females of AD. Hence, the haplogroup U inheritance may have a no outcome in Caucasian males on ageing. Elson et al. 2006 and Chinnery et al. (2004) reported studies on neuropathologically diagnosed cases of Alzheimer Disease patients with European descent and suggested that mtDNA haplogroups were not correlated with Alzheimer Disease, both by grouping together closely related or individual haplogroups.

In another study by Mancuso et al. (2007), no significant association was observed for haplogroup-associated polymorphisms as causative role of AD. They observed frequency European mtDNA haplogroups in 209 patients (unrelated) clinically diagnosed with AD and 191 controls and they were having clear Tuscan origin so that no risk of false associations between gene markers and disease should exist. They also reported that the haplogroups H, I, J, K, T, U, V, W and X do not differ significantly in the patients and control groups. In addition, both AD patients and control groups reported no significant difference between genders in terms of mtDNA haplogroup distributions. In patients with AD the ApoE4 allele as a risk factor was confirmed for AD, due to it’s significantly higher frequency than in controls although no significant association between ApoE4 alleles and mtDNA haplogroups was reported. The findings from the above study barred any significant correlation between mtDNA haplogroups, age of commencement and mean continued existence.

It can be concluded from the above review that although it has been suggested that inherited haplogroups K and U may induce Alzheimer Disease as a risk in Caucasians, but still controversial because the number of studies in different environment, region and continents are still awaited therefore, do not seem to play a major role in AD.

Parkinsons Disease:

The function of the variants at mtDNA in Parkinsons Disease has been widely studied. Van der Walt et al. (2003) studied frequency European mtDNA haplogroups by genotyping ten single nucleotide polymorphisms (SNPs) in 609 white patients with PD and 340 white controls. They reported that haplogroups J and K minimised the risk of Parkinson’s Disease with 50 % . In addition investigation elucidated that the SNP at 9055A defines haplogroup K of ATP6 minimised the probability in women and that the SNP at 13708A defining haplogroup J of ND5 gene was act as a protection for Parkinson’s Disease in persons age more than 70 years which might be due to either by the higher functioning of complex I inside the brain and in other tissues of individuals classified into lineages of J and K haplogroup having reduced ROS generations. In according to with the above described study, Pyle et al. (2005) observed and reported that the cluster of haplotypes UKJT was found to be associated with minimising the risk in population for Parkinson’s disease. Additionally, Autere et al. (2004) presumed that the possibility of PD (Parkinson’s disease) is carried totally by the non-synonymous substitutions of complex I genes in several lineages of mtDNA. They investigated this presumption by studying Finnish population and determined the number of non-synonymous substitutions in seven complex I genes of mitochondria in them. They also reported that the haplogroup supercluster JTIWX maximizes the susceptibility for Parkinson’s disease and PD with dementia both. Also, the supercluster JTIWX was significantly increase twofold risk in populations with non-synonymous substitutions in complex I subunits genes of mitochondrial DNA.

Ghezzi et al. (2005) studied the dispersal of the various mtDNA haplogroups in a huge cohort study of 620 Italian patients having PD and compared to ethnically-matched two groups of controls. They observed that the haplogroup K was correlated with a minimum probability of Parkinson’s disease and they also detailed that the 10398G polymorphism was observed to provide protection for Parkinson’s disease. The findings of Ghezzi and co-workers (2005) in terms of 10398G polymorphism was afterwards supported by Huerta et al. (2005) in 271 Spanish patients of PD and 230 controls although the correlation between haplogroup K and lower risk of PD was excluded in their study.

b) Mitochondrial DNA Haplogroups and Type 2 Diabetes:

In the secretion of insulin by pancreatic β‐cells mitochondria plays a key role and mutations of pathogenic nature in the mitochondrial DNA (mtDNA) acts as one of the causes for diabetes. The factor for occurrence of Type 2 diabetes has a powerful molecular genetics aspect in increasing the prospects of the genetic variants at mtDNA changes the susceptibility of causing the disorder. Current findings and reporting’s from various studies have put forward inconsistent results.

Chinnery et al. (2007) studied 897 cases of type 2 diabetes and 1010 population‐matched controls of UK for European mtDNA haplogroups and reported that these haplogroups are implausible to acts a key part in the probability of causing the disorder. Poulton et al. (2002) conducted small case–control investigations and described a correlation between type 2 diabetes and the 16184–16193 polyC tract a non‐coding region of mtDNA while Chinnery et al. (2005) do not confirmed the findings of Poulton et al. (2002) in a larger study by doing meta‐analysis. Furthermore, recent studies on multiple genetic association study are designed with objective to examine the consequence of commonly occurred mtDNA alternatives on the susceptibility of getting the metabolic syndrome suggested non significant proof of link between variations at mtDNA and type 2 diabetes (Saxena et al. 2006). Nearby review of the available data showed a convincing correlation between haplogroup J markers and type 2 diabetes in one population, while after modification for multiple significance testing on entire dataset no such associations were observed (Saxena et al. 2006). Crispim et al. (2006) has currently reported association of Haplogroup J and insulin resistance and type 2 diabetes in a study on 347 patients and 350 controls of Brazilian populations. Specified prospective of these findings which are inconsistent in nature, more number of studies are required to validate the findings without any controversies by recognizing the deep‐rooted ancient genetic mtDNA variants that influence the type 2 diabetes contributes towards the susceptibility for the disorder.

c) Mitochondrial DNA Haplogroups and Cardiovascular disease:

Heart failures have become a major health problem in many countries. A thorough study regarding its fundamental pathophysiology is essential to endow with initial diagnosis and enhanced remedies for precluding and avoiding the disease. It is in general now that (ROS) reactive oxygen species are concerned with several cardiovascular diseases (CVDs), for instance coronary heart disease, ischemic injury and congestive heart failures. A disparity between antioxidants and endogenous oxidants produces oxidative stress, which becomes a factor for vascular atherogenesis and dysfunction (Kojda and Harrison, 1999). In coronary arteries, Atherosclerosis (ALS) is the major reason of ischemic cardiomyopathy (IC). Pathogenesis of atherosclerosis and disease headway of coronary artery involves inflammation and ROS production as recently established vital mechanism (Kondo et al. 2009; Kobayashi, 2003). Mitochondrion as organelle is chief source of Reactive Oxygen Species for cardiomyocytes, for this reason this organelle is considered as a major player in development of ischemic cardiomyopathy. Nowadays, various researches studies and findings are reported indicating frequent mitochondrial DNA haplotypes are associated with several phenotypes with some mtDNA-linked diseases (Wallace et al. 2010; Moreno-Loshuer associated tos et al. 2006). On the other hand, the association of mitochondrial DNA haplogroups in cardiovascular diseases left unanswered and inconsistent and only some research studies are available to clarify this aspect have been carried out and approved. Such as, N9b haplogroup was reported and considered as protection as opposed to myocardial infarction in Japanese men,( Nishigaki, 2007) while in a middle European population haplogroup T reported to be associated with coronary artery disease, (Kofler et al. 2009) and currently in patients from the North of Spain reported mitochondrial DNA haplogroup H with initial inception of myocardial infarction (Benn et al. 2008). Though another European studies reported contradictory results as no association of mitochondrial haplogroups with risk of ischaemic cardiovascular disease or with any acute coronary syndromes (Benn et al. 2008; Chinnery et al. 2010).

d) Mitochondrial DNA Haplogroups and other diseases

Populations evolved autonomously with recent history of origin, haplogroups helps to distinguish such populations (Soares et al. 2012). By the mitochondrial rate of mutation the determination of the haplogroups identification is limited; while the SNPs which are located in the mitochondrial control region are particularly helpful as in this region mutation rate is quite quicker than the remaining of the mtDNA (Galtier et al. 2009). Subsequently, if a number of diseases are influenced by function of mitochondria, they will perform in a different way according to the haplogroup of the patient. Above all, in Japanese women haplogroup N9a reported to be significantly associated with the resistance to metabolic syndrome (Tanaka et al. 2007). Nardelli et al. (2013) reported association of haplogroup T as a risk factor for morbid obesity among population of southern Italy [body mass index (BMI) >45kg/m2 ]. Liou et al. (2012) described association haplogroup B4 with diabetes in Taiwanese population. Haplogroup J maximizes the probability of age related muscular degeneration in Caucasian population (Mueller et al. 2012).

The mutation of 11778 G to A or the 14484 T to C causes LOHN progression leaded visual loss due to neuropathy in individuals carrying in haplogroup J (Man et al. 2004). In some other diseases which are non- mitochondrial in nature haplogroups are reported to be associated. In patients with severe sepsis, haplogroups H and R were reported as a self-regulating interpreter of survival (Baudouin et al. 2004; Yang et al. 2005). Correspondingly, in lipoatrophy haplogroup T was observed and reported to provide protection after antiretroviral therapy given (Hendrickson et al. 2009). Although findings discussed above requires validation and conformation, the capable role of mtDNA in the classifying and arranging patients cannot be denied.

CONCLUSION:

Mitochondrion is considered as one of the atypical organelles with unconventional genetics and a extensive account of co-evolution with eukaryotes. Delicate alterations in their functional aspect could help describe the changeability of complex diseases in transverse populations and also its association with certain neurodegenerative diseases that emerge afterwards in life. Mitochondria can be promptly discriminated on the basis of analysis of mtDNA and such discrimination can be correlated with working functioning and operation of the organism. However, mitochondrial DNA studies are yet inadequate by deficient set of data and time required for it analysis as a routine marker is still not explored too much.

ACKNOWLEDGEMENT:

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

REFERENCES:

1. Autere J, Moilanen JS, Finnila S. et al. (2004). Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia. Hum. Genet. Vol. 115, pp. 29–35.

2. Baudouin SV, Saunders D, Tiangyou W, Elson JL, Poynter J, et al. (2005) Mitochondrial DNA and survival after sepsis: a prospective study. Lancet 366: 2118-2121.

3. Baudouin SV, Saunders D, Tiangyou W, Elson JL, Poynter J, et al. (2005) Mitochondrial DNA and survival after sepsis: a prospective study. Lancet 366: 2118-2121.

4. Benn M, Schwartz M, Nordestgaard BG, Tybjaerg-Hansen A. Mitochondrial haplogroups: ischemic cardiovascular disease, other diseases, mortality, and longevity in the general population. Circulation 2008; 117:2492 –2501.

5. Booker LM, Habermacher GM, Jessie BC, Sun QC, Baumann AK, et al. (2006) North American white mitochondrial haplogroups in prostate and renal cancer. J Urol 175: 468-472.

6. Carrieri G, Bonafe M, De Luca M, Rose G, Varcasia O, Bruni A, Maletta R, Nicmias B, Sorbi S, Corsonello F, Feraco E, Andreev K, Yashin AI, Francheschi C, De Benedictis G (2001) Mitochondrial DNA haplogroups and APOE4 allele are not independent variables in sporadic Alzheimer’s disease. Hum Genet 108:194–198.

7. Carrieri G, Bonafe M, De M Luca. et al. Mitochondrial DNA haplogroups and ApoE4 allele are non-independent variables in sporadic Alzheimer's disease. Hum Genet. 2001; 108:194–198.

8. Chagnon P, Gee M, Filion M. et al. Phylogenetic analysis of the mitochondrial genome indicates significant differences between patients with Alzheimer disease and controls in a French-Canadian founder population. Am J Med Genet. 1999; 85:20–30.

9. Chinnery P F, Elliott H R, Patel S, Lambert C, Keers S M, Durham S E, McCarthy M I, Hitman G A, Hattersley A T, Walker M. Role of the mitochondrial DNA 16184–16193 poly‐C tract in type 2 diabetes. Lancet 2005 3661650–1651.

10. Chinnery PF, Elliot HR, Syed A, Rothwell PM. Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: a genetic association study. Lancet Neurol 2010; 9:498 –503.

11. Chinnery PF, Taylor GA, Howell N. et al. Mitochondrial DNA haplogroups and susceptibility to AD and dementia with Lewy bodies. Neurology. 2000; 55:302–304. doi: 10.1212/WNL.55.2.302.

12. Crispim D, Canani L H, Gross J L, Tschiedel B, Souto K E, Roisenberg I. The European‐specific mitochondrial cluster J/T could confer an increased risk of insulin‐resistance and type 2 diabetes: an analysis of the m.4216T>C and m.4917A>G variants. Ann Hum Genet 200670(Pt 4)488–495.

13. Darvishi K, Sharma S, Bhat AK, Rai E, Bamezai RN (2007) Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer. Cancer Lett 249: 249-255.

14. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafe M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C (1999) Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 13:1532–1536.

15. Elson JL, Herrnstadt C, Preston G. et al. Does the mitochondrial genome play a role in the etiology of Alzheimer's disease? Hum Genet. 2006; 119:241–254. doi: 10.1007/s00439-005-0123-8.

16. Fernández-Caggiano M, Barallobre-Barreiro J, Rego-Pérez I, Crespo-Leiro MG, Paniagua MJ, et al. (2012) Mitochondrial haplogroups H and J: risk and protective factors for ischemic cardiomyopathy. PLoS One 7: e44128.

17. Galtier N, Jobson RW, Nabholz B, Glémin S, Blier PU (2009) Mitochondrial whims: metabolic rate, longevity and the rate of molecular evolution. Biol Lett 5: 413-416.

18. Ghezzi, D., Marelli, C., Achilli, A. et al. (2005), ‘Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson’s disease in Italians’, Eur. J. Hum. Genet. Vol. 13, pp. 748–752.

19. Hendrickson SL, Hutcheson HB, Ruiz-Pesini E, Poole JC, Lautenberger J, et al. (2008) Mitochondrial DNA haplogroups influence AIDS progression. AIDS 22: 2429-2439.

20. Hendrickson SL, Kingsley LA, Ruiz-Pesini E, Poole JC, Jacobson LP, et al. (2009) Mitochondrial DNA haplogroups influence lipoatrophy after highly active antiretroviral therapy. J Acquir Immune Defic Syndr 51: 111-116.

21. Huerta, C., Castro, M.G., Coto, E. et al. (2005), ‘Mitochondrial DNA polymorphisms and risk of Parkinson’s disease in Spanish population’, J. Neurol. Sci. Vol. 236, pp. 49–54.

22. Kobayashi S, Inoue N, Ohashi Y, Terashima M, Matsui K, et al. (2003) Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein. Arterioscler Thromb Vasc Biol 23(8): 1398–404.

23. Kofler B, Mueller EE, Eder W, Stanger O, Maier R, Weger M, Haas A, Winker R, Schmut O, Paulweber B, Iglseder B, Renner W, Wiesbauer M, Aigner I, Santic D, Zimmermann FA, Mayr JA, Sperl W. Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a case control study. BMC Med Genet 2009; 10:35.

24. Kojda G, Harrison D (1999) Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. vasc Res 43(3): 562–71.

25. Kondo T, Hirose M, Kageyama K (2009) Roles of oxidative stress and redox regulation in atherosclerosis. J Atheroscler Thromb 16(5): 532–8.

26. Lai CH, Huang SF, Chen IH, Liao CT, Wang HM, et al. (2012) The mitochondrial DNA Northeast Asia CZD haplogroup is associated with good disease-free survival among male oral squamous cell carcinoma patients. PLoS One 7: e49684.

27. Liou CW, Chen JB, Tiao MM, Weng SW, Huang TL, et al. (2012) Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes 61: 2642-2651.

28. Liou CW, Chen JB, Tiao MM, Weng SW, Huang TL, et al. (2012) Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes 61: 2642-2651.

29. Man PY, Howel N, Mackey DA, Nørby S, Rosenberg T, et al. (2004) Mitochondrial DNA haplogroup distribution within Leber hereditary optic neuropathy pedigrees. J Med Genet 41: e41.

30. Mancuso M, Conforti FL, Rocchi A, Tessitore A, Muglia M, Tedeschi G, Panza D, et al (2004) Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis? Neurosci Lett 371:158–162[PubMed] [Cross Ref]10.1016/j.neulet.2004.08.060

31. Mancuso, M., Nardini, M., Micheli, D. et al. (2007), ‘Lack of association between mtDNA haplogroups and Alzheimer’s disease in Tuscany’, Neurol. Sci., Vol. 28, pp. 142–147

32. Moreno-Loshuertos R, Acı´n-Pe´rez R, Ferna´ndez-Silva P, Movilla N, Pe´rez-Martos A, Rodriguez de Cordoba S, Gallardo ME, Enrı´quez JA. Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants. Nat Genet 2006;38:1261 –1268.

33. Mueller EE, Schaier E, Brunner SM, Eder W, Mayr JA, et al. (2012) Mitochondrial haplogroups and control region polymorphisms in age-related macular degeneration: a case-control study. PLoS One 7: e30874.

34. Nardelli C, Labruna G, Liguori R, Mazzaccara C, Ferrigno M, et al. (2013) Haplogroup T is an obesity risk factor: mitochondrial DNA haplotyping in a morbid obese population from southern Italy. Biomed Res Int 2013: 631082.

35. Neil Howell, Joanna L. Elson, Patrick F. Chinnery, Douglass M. Turnbull. mtDNA mutations and common neurodegenerative disorders. Trends in Genetics. Volume 21, Issue 11, p583–586, November 2005.

36. Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylha M, Majamaa K (2003) Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 112:29–33.

37. Nishigaki Y, Yamada Y, Fuku N, Matsuo H, Segawa T, Watanabe S, Kato K, Yokoi K, Yamaguchi S, Nozawa Y, Tanaka M. Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males. Hum Genet 2007; 120:827 –836.

38. P F Chinnery, C Mowbray, S K Patel, J L Elson, M Sampson, G A Hitman, M I McCarthy, A T Hattersley, and M Walker. Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls. J Med Genet. 2007 Jun; 44(6): e80.

39. Poulton J, Luan J, Macaulay V, Hennings S, Mitchell J, Wareham N J. Type 2 diabetes is associated with a common mitochondrial variant: evidence from a population‐based case–control study. Hum Mol Genet 2002 111581–1583.

40. Pyle, A., Foltynie, T., Tiangyou, W. et al. (2005), ‘Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD’, Ann. Neurol. Vol. 57, pp. 564–567.

41. Ruiz-Pesini E, Lapeña A-C, Díez-Sánchez C, Pérez-Martos A, Montoya J, Alvarez E, Díaz M, Urriés A, Montoro L, López-Pérez MJ, Enriquez JA (2000) Human mtDNA haplogroups associated with a high or reduced spermatozoa motility. Am J Hum Genet 67:682–696.

42. Samuels David C, Carothers Andrew D, Horton Robin, Chinnery Patrick F. 2006. The Power to Detect Disease Associations with Mitochondrial DNA Haplogroups. Am J Hum Genet. 2006 Apr; 78(4): 713–720.

43. Saxena R, de Bakker P I, Singer K, Mootha V, Burtt N, Hirschhorn J N, Gaudet D, Isomaa B, Daly M J, Groop L, Ardlie K G, Altshuler D. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am J Hum Genet 20067954–61.

44. Soares P, Alshamali F, Pereira JB, Fernandes V, Silva NM, et al. (2012) The Expansion of mtDNA Haplogroup L3 within and out of Africa. Mol Biol Evol 29: 915-927.

45. Tanaka M, Fuku N, Nishigaki Y, Matsuo H, Segawa T, et al. (2007) Women with mitochondrial haplogroup N9a are protected against metabolic syndrome. Diabetes 56: 518-521.

46. van der Walt JM, Dementieva YA, Martin ER, Scott WK, Nicodemus KK, Kroner CC, Welsh-Bohmer KA, Saunders AM, Roses AD, Small GW, Schmechel DE, Murali Doraiswamy P, Gilbert JR, Haines JL, Vance JM, Pericak-Vance MA (2004) Analysis of European mitochondrial haplogroups with Alzheimer disease risk. Neurosci Lett 365:28–32.

47. Van der Walt JM, Dementieva YA, Martin ER. et al. Analysis of European mitochondrial haplogroups with Alzheimer disease risk. Neurosci Lett. 2004; 365:28–32. doi: 10.1016/j.neulet.2004.04.051. [PubMed] [Cross Ref]

48. Van der Walt, J.M., Nicodemus, K.K., Martin, E.R. et al. (2003), ‘Mitochondrial polymorphisms significantly reduce the risk of Parkinson’s disease’, Am. J. Hum. Genet. Vol. 72, pp. 804–811.

49. Wallace DC, Fan W, Procaccio V. Mitochondrial energetics and therapeutics. Annu Rev Pathol Mech Dis 2010;5:297 –348.

50. Wolf C, Gramer E, Müller-Myhsok B, Pasutto F, Wissinger B, et al. (2010) Mitochondrial haplogroup U is associated with a reduced risk to develop exfoliation glaucoma in the German population. BMC Genet 11: 8.

51. Yang Y, Shou Z, Zhang P, He Q, Xiao H, et al. (2008) Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population. Genet Med 10: 187-192.

52. Yang Y, Shou Z, Zhang P, He Q, Xiao H, et al. (2008) Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population. Genet Med 10: 187-192.

Received on 02.05.2017 Modified on 18.06.2017

Research J. Pharm. and Tech 2017; 10(12): 4445-4450.

DOI: 10.5958/0974-360X.2017.00819.8

Haplogroup	Disease	References
H	Predictor of survival in severe sepsis	Baudouin et al. 2005
J, U5	Accelerated AIDS progression	Hendrickson et al. 2008
H3, UK, IWX	Protection against AIDS progression	Hendrickson et al. 2008
CZD	Good disease-free survival in Squamous cell carcinoma patients	Lai et al. 2012
R	Predictor of survival in severe sepsis	Yang et al. 2008
B4	Increased risk of diabetes	Liou et al. 2012
H	Increased risk of ischemic cardiomiopathy	Fernández-Caggiano et al. 2012
J	Increased frequency of optic neuropathy in LHON, and age related macular degeneration, Decreased incidence of ischemic cardiomiopathy	Man et al. 2004; Mueller et al. 2012; Fernández-Caggiano et al. 2012
N	Increased risk of Breast Cancer and esophageal squamous cell carcinoma	Darvishi et al. 2007
N9a	Protective for metabolic syndrome	Tanaka et al. 2007
U	Increased risk of prostate and renal cancer Reduced risk of exfoliation glaucoma	Booker et al. 2006 ;Wolf et al. 2010
T	Increased risk of morbid obesity	Nardelli et al. 2013