What specific types of genes are highly susceptible to suffer from obesity

What specific types of genes are highly susceptible to suffer from obesity?

In westernized countries especially, the accessibility of ample, energy-rich processed foods in the last few decades has resulted in a sharp rise in the occurrence of obesity. Obesity is a key risk aspect for the various disease like pulmonary diseases, cardiovascular diseases, psychiatric illness metabolic related diseases (e.g. diabetes), osteoarticular diseases, some cancer also etc.

In the 1960s, Neel gave the 'thrifty gene' hypothesis, explaining there are some genes which enable individuals to competently collect and process food to store fat when there is an abundance of food. So, during starvation time stored fat can be decomposed to provide energy to the body. People who possess these genes generally not becoming only slightly overweight, but exceptionally obese. According to USA studies, such kind of people can be seen in high-risk groups, like African-Americans, Pima Indians, Hispanic-Americans and Pacific Islanders. Scientific studies demonstrate that genetics plays a significant role in obesity. Genes can be able to cause obesity directly in some of the syndromes like Bardet-Biedl syndrome, Prader-Willi syndrome etc. Obesity is a highly complex disease with consequence of the interactions of an extensive variety of genetic and environmental factors.

It is now investigated that overweight persons and their forms are related within a family. Obesity risk increased from two to eight folds for a person with a personal family history as compared to those with no family history related to obesity. As the transfer of heredity, obesity gene may link to body fat from 5 to 40%, adipose tissue density, and occurrence rate from 40 to 55%. The increase in body weight and adipose gain upsurge with an increase in age, also affected by heredity that is ultimately linked to the gene. Incidences of monogenic types of obesity are instigated by genetic mutations. The utmost common forms of obesity are undoubtedly the outcome of variations within a large and different amount of genes. Sequence variants inside a pool of 56 different genes were reported as being linked to obesity phenotypes, however, only a few showing positive results in different studies.

Few genes associated with obesity due to monogenic effects and Mendelian disorder reported in previous years summarized below:

a.

Single-gene mutations with an obesity phenotype

Gene Name

1

Corticotropin-releasing hormone receptor

CRHR1

2

Corticotropin-releasing hormone receptor

CRHR2

3

G-protein-coupled receptor

GPR24

4

Leptin (obesity homolog, mouse)

LEP

5

Leptin receptor

LEPR

6

Melanocortin 3 receptor

MC3R

7

Melanocortin 4 receptor

MC4R

8

Neurotrophic tyrosine kinase receptor type 2

NTRK2

9

Proopiomelanocortin

POMC

10

Proprotein convertase subtilisin/kexin type 1

PCSK1

11

Single-minded homolog 1 (Drosophila)

SIM1

b.

Autosomal recessive

 

12

Alstrom syndrome

ALMS1

13

Bardet-Biedl syndrome 1

BBS1

14

Bardet-Biedl syndrome 2

BBS2

15

Bardet-Biedl syndrome 3

BBS3

16

Bardet-Biedl syndrome 4

BBS4

17

Bardet-Biedl syndrome 5

BBS5

18

Bardet-Biedl syndrome 6

MKKS

19

Bardet-Biedl syndrome

BBS7

20

Bardet-Biedl syndrome

BBS8

21

Berardinelli-Seip congenital lipodystrophy

AGPAT2

22

Berardinelli-Seip congenital lipodystrophy

BSCL2

23

Carbohydrate-deficient glycoprotein syndrome type

PMM2

24

Cohen syndrome

COH1

25

Combined pituitary hormone deficiency

PROP1

26

Fanconi-Bickel syndrome

SLC2A2

27

Isolated growth hormone (GH) deficiency

GHRHR

28

Cortisone reductase deficiency

H6PD

29

Cortisone reductase deficiency

HSD11B1

30

Severe insulin resistance with obesity

PPARG, PPP1R3A

c.

Autosomal dominant

 

31

Achondroplasia

FGFR3

32

AHO (Pseudopseudohypoparathyroidism)

GNAS

33

AHO 2

AHO2

34

Brachydactyly mental retardation syndrome

STK25

35

Angelman syndrome with obesity

ANCR

36

Anisomastia

ANMA

37

Carney complex with primary pigmented nodular

PRKAR1A

38

Familial partial lipodystrophy, Dunnigan, type 3

PPARG

39

Familial partial lipodystrophy, type 2

LMNA

40

Insulin resistance syndromes

INSR

41

Isolated GH deficiency

GH1

42

Multiple endocrine neoplasia, type 1 with Cushing's disease

MEN1

43

Posterior polymorphous corneal dystrophy (chromosome 1)

COL8A2

44

Posterior polymorphous corneal dystrophy (chromosome 20)

VSX1

45

Prader-Willi syndrome

IPW

46

Prader-Willi-like syndrome

SIM1

47

Thyroid hormone resistance syndrome

THRB

48

Ulnar-Mammary (Schinzel) syndrome

TBX3

49

WAGR syndrome with obesity

WT1

d.

X linked

 

50

Borjeson-Forssman-Lehmann syndrome

PHF6

51

Choroideremia with deafness and obesity

CHM

52

Fragile X syndrome with Prader-Willi-like phenotype

FMR1

53

Mental retardation X-linked, syndromic 7

MRXS7

54

Mental retardation X-linked, syndromic 16

MECP2

55

Mental retardation, X-linked, syndromic 11

MRXS11

56

Prader-Willi-like syndrome, X-linked

PWLSX

57

Simpson-Golabi-Behmel 1

GPC3

58

Simpson-Golabi-Behmel 2

SGBS2

59

Wilson-Turner syndrome

WTS

 

There is presently 22 gene linked to five positive and confident studies (mentioned below). These genes comprise members of the various metabolic pathway like leptin-melanocortin pathway, pro-inflammatory cytokines, and various uncoupling proteins.

Some genes related to obesity are as follows:                                                           

S.No.

Gene symbol

Full name

1

ACE

Angiotensin I-converting enzyme (peptidyl-dipeptidase A)

2

ADIPOQ

Adiponectin, C1Q and collagen domain containing

3

ADRB2

Adrenergic, beta-2-, receptor, surface

4

ADRB3

Adrenergic, beta-3-, receptor

5

DRD2

Dopamine receptor D2

6

GNB3

Guanine nucleotide binding protein (G protein)

7

HTR2C

5-hydroxytryptamine (serotonin) receptor 2C

8

IL6

Interleukin 6 (interferon, beta 2)

9

INS

Insulin

10

LDLR

Low density lipoprotein receptor (familial hypercholesterolaemia)

11

LEP

Leptin (obesity homologue, mouse)

12

LEPR

Leptin receptor

13

LIPE

Lipase, hormone-sensitive

14

MC4R

Melanocortin 4 receptor

15

NR3C1

Nuclear receptor sub-family 3

16

PLIN

Perilipin

17

PPARG

Peroxisome proliferative activated receptor, gamma

18

RETN

Resistin

19

TNF

Tumor necrosis factor (TNF superfamily, member 2)

20

UCP1

Uncoupling protein 1 (mitochondrial, proton carrier)

21

UCP2

Uncoupling protein 2 (mitochondrial, proton carrier)

22

UCP3

Uncoupling protein 3 (mitochondrial, proton carrier)

Beside these, it's also needed to understand that environment factors also playing a significant role in causing obesity. Environmental factors directly influence the activation and deactivation of the mentioned gene. Significantly identification of those genes will surely help in elucidating the etiology related to obesity and its metabolic significances. With this knowledge further it will ease the identification of their risk factor in relations of their genetic profile to develop their personalized treatment approaches.

Conclusion:

It is concluded that genes do not permanently predict future fitness. Genes and environmental factors both be required for a person to become overweight. In some cases multiple genes may upsurge one's vulnerability for obesity with required outside factors; such as lavish food supply with less physical movement. Scientists have found numerous obesity susceptibility genes and the mixture of an obesogenic atmosphere will obviously causing obesity development in any individual. Though, sometimes it is likely possible to be obese without having any role of any candidate gene. 

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