Introduction
Obesity is an excessive accumulation of body fat and in its gross manifestation poses a real threat to health. It is the most prevalent, chronic medical condition in the developed, as well as in developing countries. Epidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). This finding has potentially important health implications and warrant further investigation particularly for MTHFR gene polymorphisms to determine whether a causal relationship exists and the direction of this relationship. During the last three decades Saudi Arabia has seen a considerably rising rates for both overweight and obesity Qassim region is a tribal area in the middle zone of Saudi Arabia characteristically having high rate of consanguinity and familial diseases as obesity with diabetes and cardiovascular disorders.
The objectives of this study are to evaluate the association of polymorphisms with MTHFR and ACE genes with overweight and obesity among Saudi patients from Al Qassim region.
Methods
This study includes 130 patients with overweight or obesity and 111 normal weight controls in the 18–40 years age group. The patients’ DNA was analyzed for polymorphisms of MTHFR; 677C/T and 1298 A/C and ACE; I/D genes using real-time PCR.
Results
Genotype and allele frequencies of studied polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to that of controls (Table 1). However, on analysis of body mass index (BMI), cases showed higher mean ± SD values –although nonsignificant- among those carrying the mutant MTHFR 677 T allele (CT+TT vs. CC, 30.7±4.5 vs. 29.9±4.9), 1298 C allele (AC+CC vs. AA, 29.9±4.1 vs. 29.7± 5.5) and ACE D allele (ID+DD vs. II, 30.0±5.1 vs. 29.1 ± 2.8). In addition, controls having the DD and ID genotypes showed higher statistically significant values of BMI than those of the II genotype (22.0 ± 1.9, 21.7 ± 2.6 and 19.5 ± 2.3 respectively, p<0.05) (Table 2).
Table 1.
| Genotypes and Alleles | Overweight/Obese n (%) | Control n (%) | P (χ2) | OR (95% CI) |
|---|---|---|---|---|
| MTHFR 677 | ||||
| CC | 89 (69.5) | 69(62.7) | 0.33 | 1.4 (0.8–2.3) |
| TC | 34 (26.6) | 36(32.7) | 0.37 | 0.7 (0.43–1.3) |
| TT | 5 (3.9) | 5(4.5) | 0.94 | 0.85 ( 0.24–3.03) |
| C | 212 () | 174 | 0.36 | 1.3 (0.81–2.02) |
| T | 44 () | 46 | 0.36 | 0.79 (0.5–1.2) |
| MTHFR 1298 | ||||
| AA | 70(54.7) | 51(46.4) | 0.25 | 1.4(0.84 –2.3) |
| AC | 45 (35.2) | 47(42.7) | 0.29 | 0.73(0.43–1.23) |
| CC | 13 (10.2) | 12 (10.9) | 0.98 | 0.92 (0.42–2.12) |
| A | 185 () | 149 () | 0.33 | 1.2 (0.84–1.84) |
| C | 71 () | 71 () | 0.33 | 0.81 ( 0.54–1.19) |
| ACE I/D | ||||
| II | 12 (9.5) | 5(4.5) | 0.21 | 1.23( 0.76–6.55) |
| ID | 54 (42.9) | 44(39.6) | 0.71 | 1.14 (0.68–1.92) |
| DD | 60( 47.6) | 62(55.9) | 0.26 | 0.72(0.43–1.2) |
| I | 78 () | 54 () | 0.13 | 1.4 (0.93– 2.1) |
| D | 174 () | 168 () | 0.13 | 0.72 (0.48–1.08) |
Table 2.
| Genotypes | Overweight/obese Mean + SD | Controls Mean + SD |
|---|---|---|
| MTHFR 677 | ||
| CC | 29.9 ± 4.9 | 21.7 ± 2.5 |
| CT | 31.1 ± 4.5 | 21.8 ± 1.8 |
| TT | 28.4 ± 4.6 | 23.5 ± 0.66 |
| CT+TT | 30.7 ± 4.5 | 21.97 ± 1.8 |
| MTHFR 1298 | ||
| AA | 29.7 ± 5.5 | 21.7 ± 1.9 |
| AC | 30.3 ± 4.1 | 21.8 ± 2.5 |
| CC | 28 ± 3.9 | 22.2 ± 2.6 |
| AC+CC | 29.9 ± 4.1 | 21.8 ± 2.5 |
| ACE | ||
| II | 29.1 ± 2.8 | 19.5 ± 2.3 |
| ID | 30.2 ± 4.2 | 21.7 ± 2.6* |
| DD | 29.5 ± 5.9 | 22.0 ± 1.9* |
| ID+DD | 30.0 ± 5.1 | 21.9 ± 2.2* |
Discussion
In order to assess this association we selected cases with overweight/obesity without complications and compared them to unrelated matched controls of same ethnic background. Although no significant associations were found comparing the genotype and allele frequencies of studied genes in overweight/obese cases and controls, we observed a trend for slightly higher BMI values among subjects carrying the mutant forms of these polymorphisms particularly that of the ACE DD and ID genotypes. This was markedly manifested in male subjects. Similar finding suggesting that ACE gene polymorphisms may influence the development of weight gain with a sex difference in males and females was previously reported. On the other hand, recent reports indicate a trend towards association of ACE I/D polymorphism with hypertension but not with obesity. We conclude that there is no solid association of polymorphisms related to MTHFR 677 and 1298 and ACE I/D genes with non-complicated overweight or obesity among Saudi subjects from Qassim Region. However, we recommend a further longitudinal study for follow up and genotyping of cases that might develop obesity complications.