Now a days, ischemic heart disease remains a major cause of death and disability worldwide for both men and women.[1] Coronary artery disease is defined by the presence of a plaque in the epicardial coronary arteries. Usually, the atherosclerotic plaque narrow coronary arteries, decreasing blood flow in large-medium sized coronary arteries.[2]

Cardiovascular disease (CVD) is an atypical functioning of the heart and blood vessels of the body.[3] Heart disease (HD) is a common term for a various heart  conditions.[4] High cholesterol, obesity, Diabetes, lack of exercise, hypertension, smoking, increased age, and family history are dangerous factors for cardiovascular (or heart) disease.

Coronary heart disease (CAD) is the leading cause of death worldwide. Despite being manageable, the mortality rate is increasing in developing countries and the disease burden is likely to be doubled by 2020 in these countries. Asian population is more susceptible to heart diseases and a 50 % higher prevalence of cardiovascular diseases has been reported in South Asians.[5]

Chronic stable angina is one end of the clinical and pathological spectrum of coronary artery disease (CAD), which extends all the way to myocardial infarction and sudden cardiac death. Recent findings from a number of epidemiological studies have shown that, in addition to the traditional risk factors for coronary artery disease (CAD), such as age, male sex, hypertension, diabetes mellitus, obesity, hypercholesterolemia, smoking, and family history, factors related to lifestyle and the environment also contribute to an increased risk of developing CAD.[6] A genetic predisposition is also considered to play an essential role in the etiology of coronary artery disease (CAD), as indicated by twin and family studies. This is in addition to the causes listed above.[7]

The coronary artery disease epidemic is a significant problem for the general public's health.[8] Globally, it has been demonstrated that classical risk factors provide substantial contributions to the development of cardiovascular disease (CAD).[9] Predicting risk of coronary artery disease (CAD) and premature myocardial infarction (MI).[10] is challenging in patients without traditional risk factors.[11] This highlights the importance of analyzing the role of genetic contribution towards cardiovascular risk, as highlighted by the independent contribution of family history as a risk factor for CAD.[12]

In 2007, FTO (fat mass and obesity-associated gene) was first found out in a genome-wide association study (GWAS) for type 2 diabetes mellitus (T2DM),[13] and, about simultaneously, two other studies independently described that the fat mass and obesity-associated gene was associated with obesity (or obesity related traits) in a GWAS and a genetic companion study.[14,15]

A common genetic variant (SNP rs9939609) in the first intron of FTO gene locus has showed robust association with obese phenotype in persons of European descent,[16-18] but the outcomes have been variable amongst Asians (especially in Indians). SNP rs9939609, identified with the T to A mis-sense mutation in the first intron of the fat mass and obesity associated gene on chromosome 16q12.2, is a common variant that is studied in different populations of ethnic.

It represent the SNP widely studied in different populations of whole world because it was the SNP (rs9939609) in the original European adult study and had one of the powerful relationship with BMI, with the Odds Ratio (OR) of 1.67 [Confidence Interval (CI) 1.47-1.89], for the homozygous A allele condition.[19] Relationship of  FTO SNPs with obesity has been also continuously observed in other European origin population, like French.[20]

Although research on large populations have found that various genetic differences contribute to the inherited risk of coronary artery disease (CAD), the precise identification of the candidate genes and the amount of their influence on the pathophysiology of the illness are not well established. Multiple epigenetic studies as well as high throughput, large scale genome-wide association studies (GWAS) using dense genotyping chips that contain sets of thousands of single nucleotide polymorphisms (SNPs) for whole genome assessment of genetic variants associated with common complex disease traits have identified several chromosomal loci that are associated with the risk of coronary artery disease (CAD).[21]

It has been determined that the most significant locus that shows a substantial connection with coronary artery disease (CAD) and acute myocardial infarction (AMI) is located on the chromosome 9p21. The Wellcome Trust Case-Control Consortium (WTCCC) study (8) and the German Myocardial Infarction (MI) Family Study conducted a combined analysis that uncovered additional loci for increased susceptibility and risk of coronary artery disease (CAD) at 9p21, 6q25.1, and 2q36.3. The leading SNPs for each of these loci were rs1333049, rs6922269, and rs2943634 respectively.21

Other genome-wide association studies (GWAS) carried out in Canadians (rs10757274, rs2383206)[22] and in an Icelandic population (rs1333040, rs2383207, rs10116277, and rs10757278) have found similar relationships between SNPs in the 9p21 region and CAD.[23]The associations between novel SNPs in the 9p21 genomic region and coronary artery disease (CAD) have also been replicated in large scale studies carried out in Caucasian populations,[23-25] Korean populations,[26-28] Japanese populations,[29,30] Chinese populations,[31-35] Italian populations,[36] Indian populations,[37] German populations,[24] Swedish populations,[38] British populations,[39,40] and other European populations.[41-45] Therefore, even though several candidate SNPs on chromosome 9p21 that are risk alleles for coronary artery disease have been found by GWAS in various large populations, the underlying processes that contribute to coronary artery disease and acute myocardial infarction have yet to be understood.

APOA5 rs2266788 (C) is a polymorphic variation allele that inhibits the binding capacity of miR-3201, which is positioned at the APOA5 3'UTR. As a result, it raises the APOA5 plasma level by preventing the degradation of APOA5 mRNA, which is related with the degree of stenosis.[46] There is evidence that the genetic variations rs10455872 (G) and rs3798220 (C) of the LPA gene are related with coronary artery disease (CAD). Polymorphism rs10455872 has been shown to be related with an increased risk of coronary artery disease in a number of different groups.[46]

On the other hand, reports of links with rs3798220 have been inconsistent. The non-synonymous features of rs3798220 encourage the substitution of isoleucine to methionine (I4399M) in the protease-like domain of Apo-A, which in turn confers a risk for severe coronary artery disease.[46] In a variety of groups and cohort studies, the correlation between the 9p21 inhabited polymorphism, rs1333049 and rs2383207, and coronary artery disease (CAD) or the severity of CAD has been demonstrated.[46]

This cross-sectional observational study entitled “A Molecular Analysis of FTO Gene Polymorphism in Patients of Coronary Artery Disease in Different Socio-Economic Demography of North Indian Population” was conducted after clearance from Board of Studies and Ethical committee in the Department of Department of Anatomy, Swami Vivekanand Subharti University, Subharti Medical College, Meerut.

METHOD OF COLLECTION OF DATA

Sample size calculation

Sample size has been calculated in order to subjects of having cardio vascular disease. Assuming a minimum power 80% and 95% significance level the sample size has been calculated using this formula:

(formula is available in pdf)

• p- Incidence of the disease (obesity)
• (p1-p2)2 or d2 – Is the difference which we want to detect at a specified power & level of confidence.
• Zβ - power of statistical test we want to be minimum 80% for which is Zβ is 0.84.
• Zα/2 –is the level of confidence we have chosen 95% confidence in this Zα/2=1.96.

STUDY POPULATION

The study population was chosen as per the inclusion and exclusion criteria

Inclusion Criteria

1. Subjects between 30 -60 years
2. Subjects of either sex having coronary artery diseases.
3. Subjects having signs and symptoms of CVD.
4. Subjects having primary obesity.

Exclusion Criteria

1. Subjects below 30 years and more than 60 years.
2. Subjects having severe congenital cardiac anomalies.
3. Subjects who undergone bypass surgery.
4. Obesity produced due to certain secondary cause.
5. Subjects suffering from any grave disease and hospitalization in last 3 months.
6. Endocrinal origin obesity.
7. Subjects who are not willingly to participate in the study.

METHODOLOGY

Sampling:-

• Trans-luminal diameter and vascular pattern of coronary artery were measured in angiogram of subjects having coronary artery diseases. Coronary arterial dominance is defined by the vessel which gives rise to the posterior descending artery (PDA), which supplies the myocardium of the inferior 1/3rd of the interventricular septum.[22]
• The diameter of the coronary artery also were measured in angiogram. The proximal left main (LM), the left anterior descending (LAD), left circumflex (LCx), and the right coronary artery (RCA) were measured.
• 5ml of venous blood were drawn from peripheral vein using Di sodium EDTA vacutainers. All the samples were aliquoted and stored at -800 C until tested.
• All the samples have their FTO gene were analyzed for the sequence of intron 1 of chromosome16q12.2 SNP rs9939609.

The Procedure to obtain the FTO polymorphism is:-

▪ Isolation of DNA

▪ Molecular characterization of polymorphism of FTO gene by Polymerase chain reaction

▪ Agarose gel electrophoresis

Statistical analysis

After the data were put into the spreadsheet using Microsoft excel, the statistical analysis was carried out using the statistical programmed SPSS version 25.0. The information pertaining to the quantitative variables (numerical variables) was presented in the form of the mean and standard deviation, whereas the information pertaining to the qualitative variables (categorical variables) was presented in the form of the frequency and percentage of each category.

The student t-test was applied for the purpose of analyzing the differences in mean values between the two groups, while the chi-square test was utilized for the purpose of analysing the frequency differences between the two groups. If the p-value was less than 0.05, then it was considered to be statistically significant. If the p-value was more than 0.05, then it was not.

Table 1: Describing the study groups as per Age (yrs)

The comparison of mean age between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.

Table 2: Describing the study groups as per Gender analyzing the FTO gene polymorphism.

The comparison of distribution of Gender between A-A, A-T and T-T groups using the chi-square test showed that the A-A was significantly more among males.

Table 3: Describing the study groups as per

The comparison of distribution of Coronary dominance between A-A, A-T and T-T groups using the chi-square test showed that the Right dominance was significantly more among A-A group.

Table 4: Describing the study groups as per BMI (kg/m2) of subjects having coronary artery disease.

The comparison of mean BMI between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.

Table 5: Describing the study groups as per Pulse rate

The comparison of mean Pulse rate between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.

Table 6: Describing the study groups as per Respiratory rate

The comparison of mean Respiratory rate between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.

Table 7: Describing the study groups as per Lipid profile of subjects having Coronary artery disease .

The comparison of mean TC, TG, HDL, LDL, VLDL, LDL/HDL and TC/HDL between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups. Mean Total cholesterol, LDL, VLDL and LDL/HDL was significantly more among A-A compared to A-T group which was significantly more among T-T group.

Table 8: Describing the study groups as per

The comparison of mean Atherogenic Index of Plasma (mmol/L) between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test showed that the mean Atherogenic Index of Plasma (mmol/L) was significantly more among A-A and A-T groups compared to T-T group.

Summary - The study findings can be summarized as follows:

• The comparison of mean BMI between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.
• The comparison of mean Pulse rate between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.
• The comparison of mean Respiratory rate between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups.
• The comparison of mean TC, TG, HDL, LDL, VLDL, LDL/HDL and TC/HDL between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test did not show significant difference between A-A, A-T and T-T groups. Mean Total cholesterol, LDL, VLDL and LDL/HDL was significantly more among A-A compared to A-T group which was significantly more among T-T group.
• The comparison of mean Atherogenic Index of Plasma (mmol/L) between one-way ANOVA test with inter-group comparison using the post-hoc bonferroni test showed that the mean Atherogenic Index of Plasma (mmol/L) was significantly more among A-A and A-T groups compared to T-T group.
• The comparison of distribution of Coronary dominance between A-A, A-T and T-T groups using the chi-square test showed that the Right dominance was significantly more among A-A group.

CAD is a complicated, multifaceted cardiovascular illness that is caused by a combination between hereditary and environmental risk factors. GWAS provides an ideal technique for a comprehensive genome assessment of the genetic variations linked with prevalent, complicated illnesses, such as CAD. Globally, CAD is regarded as one of the most prevalent causes of mortality, impacting 3.8 million men and 3.4 million women.80

GWAS indicates a strong connection in diverse populations between the 9p21 nucleotide sequence and the prevalence of CAD. This locus comprises of ANRIL, a non-coding tract of antisense RNA and no protein-coding genes.81 Advances in molecular and biochemical methods have altered our knowledge of CVD and CAD-causing metabolic diseases. In addition, GWAS and meta-analysis studies also uncover various disease-causing genes that are further associated and linked to the molecular foundation of CAD disorders.39

It has been hypothesized that the FTO gene variation may impact the risk of type 2 diabetes in a manner that is independent of BMI in both Europeans and East Asians [5,7]. Doney et al.[8] first demonstrated that the A allele of rs9939609 in the FTO gene increased the risk of myocardial infarction in 4,897 patients with T2D in the prospective study. This increase in risk was independent of BMI, glycohemoglobin, mean arterial pressure, HDL-C, triglycerides, and total cholesterol. This finding is relevant to the association between the FTO gene and the risk of cardiovascular disease (CVD). Research[9-16] has showed that contradicted one another. There was a strong relationship between the FTO gene variation and the risk of cardiovascular disease. This link was independent of BMI and other traditional risk factors for cardiovascular disease.(Liu)

Age

In current study work, mean age did not show significant difference between A-A, A-T and T-T groups. The mean age among A-A, A-T and T-T groups was 51.58±6.99 years, 49.12±6.71 years and 49.38±8.69 years respectively. Çakmak et al.[21] showed that in terms of age (p = 0.147), and body mass index (p = 0.058), there were no significant difference found between the patient group and the control group. Kashyap et al.[46] observed that there was a statistically significant difference between patients and controls in terms of both mean age.Bogari et al.[76] stated that the patients with CAD had a mean age (SD) of 59.04 (5.19) andAge-matched subjects in the control group.

 Gender

In present study, the comparison of distribution of Gender between A-A, A-T and T-T groups using the chi-square test showed that the A-A was significantly more among males.There were 65.7% males and 34.3% females among study population. Kashyap et al.[46]observed that there was a statistically significant difference between patients and controls with respect to gender. Bogari et al.[76] stated that the patients with CAD were 66% male and 45.4 percent male were the subjects in the control group.

Güçlü-Geyik F et al.[77] stated that there was not a significant difference found between the gender in terms of the distribution of genotypes or the frequencies of alleles. When the distributions of genotypes were compared in paired groups, it was found that there was no significant connection between the sexes in either men or women.

BMI

In our investigation, mean BMI did not show significant difference between A-A, A-T and T-T groups. Çakmak et al.[21] showed that body mass index (p = 0.058) did not differedsignificantly between the patient group and the control group.

Allele distribution

We discovered that T-T and A-T were the dominant alleles in our investigation. Güçlü-Geyik F et al.[77] indicated that the genotype distribution of the ITLN1 Val109Asp polymorphism was 56.8 percent for the AA genotype, 34.7 percent for the AT genotype, and 8.5 percent for the TT genotype. T, an uncommon allele, was found to have a frequency of 0.26 in this group of participants, according to the research.

Lipid profile

In present research work, mean Total cholesterol, LDL, VLDL and LDL/HDL was significantly more among A-A compared to A-T group which was significantly more among T-T group. The FTO rs17817449 strongly impacted the indicators of dyslipidemia and glycemic control in the investigation by Abdulhussein et al.[82] The FTO gene rs17817449 was found to have significant impacts on glycemic indicators and serum lipid profile. Because of these effects on serum lipids, insulin, and glucose levels, the FTO gene can be utilized to predict the onset of diabetes in the obese Iraqi population.

In addition, Mehrdad et al.[] found FTO rs9939609 risk allele was connected to greater leptin levels as well as lower HDL-c levels. Lappalainen et al.[31] discovered that persons who had the A-allele of rs9939609, particularly those with the AA genotype, had a lower HDL-c level (p = 0.007) when compared to individuals who had the TT genotype. The A-allele of the FTO rs9939609 polymorphism was related with lower HDL-c (p = 0.008) and higher TG level (p = 0.007) in patients with diabetes. Additionally, the risk of cardiovascular disease was raised in carriers of the A-allele.[32](Mehrdad et al)

Kashyap et al.[46] observed that patients diagnosed with coronary artery disease had a significantly higher prevalence of traditional risk factors such as diabetes, current smoking, prior history of smoking, tobacco chewing and prior history of tobacco chewing, in addition to a significantly lower HDL mean value (32.8±9.1 vs 38.3±10.3) than controls.

According to Guclu-Geyik F et al.,[77] substantial impacts of the Asp/Val+Val/Val genotype were shown to exist on fasting higher TG (p = 0.002) and lower HDL-C (p = 0.044) levels in women who did not have CAD, as well as higher LDL-C (p = 0.047) levels in males who did have serious CAD. The univariate analysis that was adjusted for age, smoking status, the presence of diabetes, and the use of lipid-lowering drugs showed that genotypes are linked with fasting levels of TG, HDL-C, and LDL-C. This was shown to be the case even after taking into account the other factors.

The Val109Asp polymorphism has not been shown to have any connection with total-C, LDL-C, HDL-C, or triglyceride levels, according to the findings of previous research that investigated the influence of this polymorphism on CAD. CAD patients with the Asp/Val genotype of the Val109Asp polymorphism were shown to have lower levels of LDL-C in studies.[83-85]

xIt was shown by Guclu-Geyik F et al.[77] that the Asp/Val+Val/Val genotype was associated with increased LDL-C in males with serious CAD. This was the case regardless of age, smoking status, the presence of diabetes, or the use of lipid-lowering medications. The fact that female carriers of the Val allele had higher LDL-C levels was not statistically significant, despite the fact that these levels were determined to be elevated. According to research that was conducted in the past, the impact that LDL-C has on the progression of cardiovascular disease is greater in males than it is in women.[86] On the other hand, it was discovered that LDL-C levels were greater after menopause, and it was reported that women over the age of 65 had a higher average of LDL-C than males had.[87]

However, contrary to our findings, Mielcarska et al.[78] in their research work found no connection between the FTO gene rs17817449, lipid parameters, or problems with glucose metabolism.

Modulation of plasma triglycerides with rs2266788 has been reported from Caucasian,[88,89] African-American,[88,90] and Hispanic populations,[90] as well as Japanese.[89,91] Patients who have stable coronary artery disease and possess the homozygous mutant allele (CC) of the polymorphic polymorphism rs2266788 have an increased risk of both unstable angina and myocardial infarction. The functional knowledge of the non-gene annotated locus 9p21.3 was strengthened as a result of the relationship between genetic variation rs1333049 and propensity to CAD.

Risk of Cardiovascular disease

We found that in our study that mean Atherogenic Index of Plasma (mmol/L) was significantly more among A-A and A-T groups compared to T-T group. Mean Diameter of Right and Left coronary artery in mm was significantly more among T-T compared to A-T which was significantly more among A-A.

Çakmak et al.[21] showed that the presence of these risk alleles brought to an increase in cardiovascular disease susceptibility of 35% and 42%, respectively. According to the findings given by McPherson et al.,[22] 20-25 percent of homozygotes for the risk allele had an elevated risk of coronary artery disease (CAD) of roughly 30-40 percent. Nearly half of the subjects in the European descents studied by Helgadottir et al.[23] and Schunkert et al.[24] were found to carry at least one high-risk allele, and the other 20-25 percent were found to carry two high-risk alleles. These individuals had a greater chance of developing coronary artery disease by 20-40 and 40-70 percent, respectively.[40,92] During the course of this research, it was discovered that variations of the risk allele A of rs2383207 and the risk allele G of rs1333049 were present in 39.3 percent and 48.2 percent of CAD patients, respectively.

Kashyap et al.[46] evaluated the association of highly associated genetic polymorphisms 2266788, rs3135506 (11q23; APO-A5), rs10455872, rs3798220 (6q26; LPA) and rs1333049, rs2383207 (9p21.3) with occurrence of CAD, severity of CAD and presentation of CAD in North Indian population. The findings offered considerable support for the contribution of the 9p21.3 variation rs1333049 to risk assessment of susceptibility to coronary artery disease as well as the severity of the condition. According to research by Cui et al., the genetic variation rs2266788 (C), which causes higher levels of TG in people who have the polymorphic allele, may have contributed to the development of coronary artery disease (CAD). It is possible to explain the triglyceride-mediated increased susceptibility of rs2266788 for CAD by referring to the cis-acting capacity of this variant for APOA5 gene expression.[93] Bhanushali AA and colleagues.[94] found a correlation between the genetic variation rs1333049 and coronary artery disease in the Western Indian population. The link between genetic variation rs1333049 and the prospective risk of CAD (Samani et al., 2007; Schunkertet al., 2008) severity of CAD and MI was discovered using GWAS.

The connection between the rs2383207 (A) risk allele and coronary artery disease, the severity of coronary artery disease, and the appearance of coronary artery disease. severity of CAD and MI, according to Schunkert et al.[24] The authors Chen SN et al.[95] reported that the genetic variant rs3135506 (AG) was associated with the severity of coronary atherosclerosis. Kashyap et al.[46] stated that the risk allele frequency of the polymorphic variation rs3135506 (G) of APOA5 was lower (0.7% of the population) than it was in other populations. This was recorded at a rate of 1-3 percent among Chinese and Japanese, 6-8 percent among Caucasians, and 15 percent among Hispanics. Among African Americans, the rate ranged from 4-8 percent.

In individuals who had metabolic syndrome, Shang et al.[96] found that serum ITLN-1 levels were independently and adversely linked with the existence and angiographic severity of coronary artery disease (CAD). In addition, the expression of ITLN1 in epicardial adipose tissue close to coronary stenotic segments was lower in individuals with CAD who had coronary artery disease than it was in non-stenotic segments.[97]

Carrying the Val allele increases the risk of catastrophic coronary artery disease (CAD) in females. This risk is independent of age, smoking, the presence of diabetes, and drug use, and it is caused by an increase in stenosis. In males, however, this impact of the allele was not seen. Independent of age, diabetes, cigarette usage, and statin use, the findings of our study demonstrate that the Val109Asp polymorphism has an influence on the severity of CAD via increasing stenosis. The high risk of critical coronary artery disease in women who carry the Val allele may be due to the fact that ITLN-1 interacts with cytokines such as adiponectin and increases stenosis via the mechanism of inflammation. This is distinct from other mechanisms such as obesity, impaired glucose tolerance, or dyslipidemia, as no association was found between any of these parameters and the critical CAD risk.[97]

It has not been determined how exactly the FTO variation is linked to an increased risk of cardiovascular disease (CVD). It is well knowledge that the FTO protein is extensively expressed in the nervous system, which is known to have a role in the regulation of the metabolic process of energy.[24] In point of fact, the FTO gene variation is shown to have an effect on the consumption of energy-dense foods rather than on the control of energy expenditure.[25] In addition, the FTO variation has been linked to diabetes-related metabolic characteristics (such as higher fasting insulin, glucose, and triglycerides, as well as lower HDL cholesterol), however this connection was eliminated when BMI was taken into account.[26](Liu)

Other research has showed that the FTO variation is connected to an elevated risk of developing hypertension by way of the regulation of sympathetic modulation of vasomotor tone.[27] Hubacek et al.[11] considered that the FTO variation may raise the risk of CVD through another mechanism, namely through its likely influence on DNA methylation. This belief is noteworthy because it suggests that the FTO variant could be responsible for the increased risk. To put it another way, the FTO gene variation may interact with an unhealthy lifestyle (such as a diet rich in fat and a lack of physical activity), which may then disrupt the epigenetic state[11] and eventually lead to the development of cardiovascular disease (CVD).(Liu)

Gene interactions and environmental influences may play distinct roles in the development of complex cardiovascular disorders like coronary artery disease (CAD) in various populations. In the north Indian population, the polymorphic variations rs2266788 (C); (APOA5) and rs1333049 (C), rs2383207 (A); (9p21.3) confirmed the connection with CAD, its severity, and its various presentations. In stable CAD patients, the variation rs2266788 may also show its connection with MI susceptibility.

To fully understand the molecular mechanism underlying the association and to assign a pathophysiological role to the FTO chromosome variants in the etio-pathology of coronary artery disease (CAD), multiple and different SNPs in this chromosomal region should be studied to elucidate the exact identity of the candidate genes and the quantity of their effect on the CAD pathogenesis. We have further shown that the three risk alleles have interdependent variable risk for CAD when used to create haplotypes. It is need to conduct more research with a larger sample size to determine the association between the risk of cardiovascular illnesses and the SNP in the FTO gene at rs17817449.

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