Abstract: peptide that acts as a neurotransmitter in the

Abstract:

Consanguineous marriages are defined as union between
the couples who has close blood relation within the family and obesity is a
condition characterized by an accumulation of excess fat deposited in the
adipose tissue of the body, which leads to increased health problems. Neuropeptide
Y (NPY) is a peptide that acts as a neurotransmitter in the human diseases and
obesity is connected with these genes. However, earlier studies have shown the
connection between NPY gene and obesity in the global ethnic populations and
there are no studies have been documented in the Saudi population. So, the
current study aims to assess relationship between first-cousin consanguineous offspring
with obesity and NPY gene polymorphism studies in the Saudi
population. In this study we will be selecting 200 subjects; 100 first cousin
offsprings of consanguineous obesities and 100 healthy controls subjects. Blood
samples will be collected from all the selected Saudi participants and genomic
DNA will be extracted with the help of commercial kits and obesity related
primers in the NPY gene will be selected and polymerase chain reaction-
restriction fragment length polymorphism analysis will be performed and
followed by 3% agarose gel electrophoresis. Statistical analysis will be
performed with SPSS software between the cases and controls. From this current
study, we try to rule out the relation between NPY gene in the first-cousin
offsprings in the consanguineous obesity in the Saudi population.

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Keywords: First-cousin, Consanguinity, NPY
gene, Saudi population

 

 

1.Introduction:

Consanguineous
marriages are common in ethnic global populations and majorly in the gulf
countries especially in first and second cousins. To mention a few examples:
the prevalence of consanguinity in Jordan was reported 35% (ISLAM, 2017). Also
in Qatar was reported 54.0% (Bener A1, 2006), in the United Arab Emirates was
50.5% as well as in Yemen was 40% (Jurdi, 2003). In Saudi Arabia, especially
the Madinah with high prevalence rate about 67.2% and low prevalence rate such
as Al-Baha with rate about 42.1% (El-Mouzan, 2007).

Obesity is a condition characterized
by an accumulation or excess of fats deposited in the adipose tissue of the
body, which leads to increased health problems. In general, obesity is
associated with diseases such as dyslipidemia, hypertension, insulin resistance,
type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) such as
hypertension, coronary heart disease (CHD) and stroke as well as gall bladder
diseases. The incidence and prevalence of obesity are increase rapidly in the
population world. As an imbalance between energy intake and energy expenditure
(utilization) will leads to the Obesity. Obesity mainly called polygenic
because results from a complex interaction between more than a gene and the
environment. Although these genes will not cause Obesity directly, but they can
affect the development of obesity in some environments with genetic
alterations. Genome-Wide Association Studies (GWAS) studies have investigated
Single Nucleotide Polymorphisms
(SNPs) associated with obesity and fat distribution (Tomei, 2015).

 

 

 

2.Literature
Review:

2.1
Consanguinity:

Consanguinity is
a Latin word derived from (i) “con” means shared and
(ii) “sanguineous” means blood and it is used to describes
relation between two individuals. Consanguineous marriages are defined as the
union between the couples who are related closer to the second cousins (Hamamy, 2012). The prevalence of inbreeding
is varied throughout the global population. In the United States,
consanguineous marriages are prohibited by law in most of the states. The rate
of consanguinity in Europe is less than 0.5%
(Bittles, 2008).  In the Gulf region, many studies have been
reported a prevalence of more than 50% in Qatar, Kuwait, and the United Arab
Emirates (Bener A1, 2006).

2.2
Prevalence:

In
Saudi Arabia, the prevalence of consanguinity was studied in thirteen
provinces, including the urban and rural areas. The rate of prevalence of the
consanguinity types was found to be 56%. In addition to the above, this
rate has been categorized by the degree of the Marital relationship. The rate
of the prevalence of first degree cousins was 33.6%, while the
prevalence of the consanguineous marriages of other types was 22.4%.
It found also the prevalence of consanguinity in the rural areas had a higher
than in urban areas (El-Mouzan MI, 2007).
A similar result was reported in Pakistan, which involved similar cultural and
tribal traits to Saudi Arabia, where two-thirds of the married people or
individuals are from consanguineous marriages. The predominant factor in
favoring consanguinity was mainly due to sociocultural reason. Also, there are
other factors such as dowries are less expensive, cultural traditions and
consolidation of family bonds (Omar A. Alharbi,
2015). Several studies have been shown the relationship between
consanguineous marriages and inherited diseases in offspring. An earlier study
from Saudi Arabia investigated the relation between the prevalent consanguinity
with common genetic diseases. Earlier studies have documented the congenital
heart diseases were strongly associated with inbreeding. In consanguineous
marriages, Offspring have a high probability to be acquiring homozygous
deleterious inherited factors, and thus leads to be have a higher possibility
of developing the autosomal recessive disorders. For example, a study reported
that increase in the risk to having a child with a recessive disorder is
related to first-cousin marriages (Hamamy H,
2011).

2.3 Incidence:

Consanguineous marriages have the highest
prevalence in the Middle East.
Thus, the attitude towards
consanguineous marriages in different studies was reported to be favorable. In
Qatar, the women were reported to have a
more positive attitude than males to consanguineous marriages (Sandridge AL, 2010). In Palestine, was found
a positive attitude in a quarter of interviewed respondents (Jaber L, 2005). The issue in a worldwide is
the consanguinity, but in the Middle East particularly. The country was
classified as the second highest in Arab country to have a high rate of
consanguineous marriage is the Kingdom of Saudi Arabia, with the prevalence
from 22–55% varying in different studies (Omar
A. Alharbi, 2015). In most of the studies on Saudi population was
reported the rates of the consanguinity is above 50% and the major
cause is first cousin marriages (Arjumand Sultan
Warsy, 2014).

2.4
Obesity:

Obesity
is also defined through the body mass index (BMI). Commonly used parameter for
classifying various degrees of adiposity (Ofei,
2005). The BMI can be measures by dividing the bodies weight in
kilograms and height in meters squared (kg/m2) called BMI. The World
Health Organization (WHO) classified adult males or females with a BMI of 25 to
29.9kg/m2 as overweight, whereas obesity categorizes according
to stages or grades to Grade 1: BMI 30.0-34.9, Grade 2: BMI 35.0-39.9 and Grade
3: BMI ?40.0 (Güngör, 2014).

Obesity
in the Saudi Arabia has the highest percentage about 33% in the world (WHO, 2017). Obesity has multifactorial
condition affected by genetic and non-genetic factors. In the adults the
overweight state is generally caused by a lack of physical activity,
uncontrolled diet leads to an excess energy intake or a combination of these
two leads to excess in energy (Güngör, 2014). In the previous studies of obesity
on Ghanaian Urban residents had higher BMI compared to rural residents. Leptin
is a protein hormone which predominantly expressed via adipocytes; to play a
significant role in saving the maintenance of the weight. Leptin normally works
on receptors on a part in the brain called hypothalamus to avoid food
consumption by counteracting the effects of potent feeding stimulants such as
neuropeptide Y. Compared obese individuals with those non-obese the obese will
have higher leptin levels (Ofei, 2005).

2.5
Genetic:

Till
now, there are no genetic studies have been documented in the kingdom. Recent
trends and improvement in the molecular diagnosis, several advanced techniques
such as next-generation sequencing, exome sequencing and whole exome sequencing
has become the landmark for the diagnostic tool in the analyzing the disease.

 

 

2.6 NPY Gene:

Neuropeptide Y (NPY) gene has
a significant role in the regulation of satiety, reproduction, central
endocrine and cardiovascular systems. Also, NPY has acute effects on feeding
behavior and energy utilization (Bhaskar, 2010).

Aim:

The current study was to assess the
relationship between first-cousin offsprings with obesity and NPY gene
polymorphism studies in the Saudi population.

 

 

 

 

 

 

 

 

 

 

 

 

 

3. Material and Methods:

3.1 Selection of subjects:

In this study we will be selecting
200 subjects; 100 consanguineous obesities and 100 healthy controls subjects
from King Saud University, Riyadh, Saudi Arabia. The inclusion criteria
for consanguineous cases are based on the first cousin siblings with obesity and
exclusion criteria comprises non-consanguineous and those are non-Saudi
subjects. Inclusion criteria for controls include non-consanguineous and not
obese subjects.  

3.2 Sample collection:

From 200 participants; 5 mL of the
venous blood will be collected and divided them into 3 mL for biochemical
analysis and 2 mL for molecular analysis.

3.3 Genetics analysis:

Blood samples which will be collected
in EDTA tubes will be used for extraction of genomic DNA using specific
commercial kits. DNA samples will be stored at ?80 °C for the further
analysis. Extracted DNA will be quantified using NanoDrop. Polymerase chain
reaction (PCR) will be carried out on Thermal Cycler (Applied Biosystems,
Hercules, California, USA) with initial step is denaturation at 95 °C for
5 min followed by 35 cycles, with each cycle containing denaturation
at 95 °C for 30 s, annealing at standardized temperatures for
30 s, extension at 72 °C for 45 min, and final extension at
72 °C for 5 min.

3.4 Sanger sequencing:

Sanger sequencing will
be performed for 30% of the samples in this study to cross check the results
and this will be applied as quality control analysis.

3.5 Statistical analysis:

Statistical analyses will be
performed with the statistical package for the social sciences (SPSS) software.
Clinical characteristics of all the subjects were expressed as mean ± SD and
t-test will be performed between the cases and controls. Odds Ratio’s (OR’s), 95%
confidence intervals (95%CI’s) and p-values will be calculated between the
cases and controls. Hardy-Weinberg Equilibrium will also be calculated in this
study.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References:

1.      Arjumand Sultan Warsy, M. H.-J.-D. (2014, June).
Is consanguinity prevalence decreasing in Saudis?: a study in two generations.
Retrieved from African Health Sciences:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196414/

2.      Bener A1, A. K. (2006, March). Consanguineous
marriage in a newly developed country: the Qatari population. Retrieved from
Journal of biosocial science.: https://www.ncbi.nlm.nih.gov/pubmed/16490156/

3.      Bhaskar, L. V. (2010, June 09). Neuropeptide Y
gene polymorphisms are not associated with obesity in a South Indian
population. Retrieved from Nature News:
http://www.nature.com/articles/ejcn201074

4.      Bittles. (2008, Aug 5). A community genetics
perspective on consanguineous marriage. Retrieved from Community genetics.:
https://www.ncbi.nlm.nih.gov/pubmed/18690000

5.      El-Mouzan. (2007, December). Regional variations
in the prevalence of consanguinity in Saudi Arabia. Retrieved from Saudi
medical journal.: https://www.ncbi.nlm.nih.gov/pubmed/18060221

6.      El-Mouzan MI, A.-S. A.-H.-O. (2007, December).
Regional variations in the prevalence of consanguinity in Saudi Arabia.
Retrieved from Saudi medical journal.:
https://www.ncbi.nlm.nih.gov/pubmed/18060221/

7.      Güngör, N. K. (2014, September). Overweight and
Obesity in Children and Adolescents. Retrieved from Journal of Clinical
Research in Pediatric : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293641/

8.      Hamamy. (2012, July). Consanguineous marriages:
Preconception consultation in primary health care settings. Retrieved from
Journal of Community Genetics:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419292/

9.      Hamamy H, A. S.-S. (2011, September).
Consanguineous marriages, pearls and perils: Geneva International Consanguinity
Workshop Report. Retrieved from Genetics in medicine : official journal of the
American College of Medical Genetics.:
https://www.ncbi.nlm.nih.gov/pubmed/21555946/

10.  ISLAM, M. M. (2017, August). CONSANGUINEOUS
MARRIAGE IN JORDAN: AN UPDATE. Retrieved from researchgate:
https://www.researchgate.net/publication/319045209_CONSANGUINEOUS_MARRIAGE_IN_JORDAN_AN_UPDATE

11.  Jaber L, R. O. (2005, June). The Journal of
adolescent health : official publication of the Society for Adolescent
Medicine. Retrieved from Awareness about problems associated with
consanguineous marriages: survey among Israeli Arab adolescents.:
https://www.ncbi.nlm.nih.gov/pubmed/15909361/

12.  Jurdi. (2003, January). The prevalence and
correlates of consanguineous marriages in Yemen: similarities and contrasts
with other Arab countries. Retrieved from Journal of biosocial science.:
https://www.ncbi.nlm.nih.gov/pubmed/12537152

13.  Ofei, F. (2005, September). Obesity – A
Preventable Disease. Retrieved from Ghana Medical Journal:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1790820/

14.  Omar A. Alharbi, W. A.-S.-H.-M. (2015). Attitude
of Saudi Arabian adults towards consanguineous marriage. Retrieved from Qatar
Medical Journal: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719437/

15.  Sandridge AL, T. J.-K. (2010, January).
Consanguinity in Qatar: knowledge, attitude and practice in a population born
between 1946 and 1991. Retrieved from Journal of biosocial science.:
https://www.ncbi.nlm.nih.gov/pubmed/19895726/

16.  Tomei, S. (2015, Apr 13). Journal of
Translational Medicine. Retrieved from Obesity susceptibility loci in Qataris,
a highly consanguineous Arabian population:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422146/#CR5

17.  WHO. (2017, March 12–16). Joint ExtErnal
Evaluation. Retrieved from World Health organization: http://apps.who.int/iris/bitstream/10665/258695/1/WHO-WHE-CPI-2017.25.report-eng.pdf?ua=1