THE +3953 (C->T) POLYMORPHISM OF INTERLEUKIN-1β GENE IN MYOCARDIAL INFARCTION IN TATARS AND RUSSIANS FROM BASHKORTOSTAN
Tulyakova G1,*, Nasibullin T1, Zakirova A2, Khusnutdinova E1, Mustafina O1
*Corresponding Author: Dr. Gulnara Tulyakova, Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, October Avenue 69, 450054 Ufa, Bashkortostan, Russia; Tel.: +7-3472-361176; Fax: +7-3472-356100; E-mail: gulnarat@mail.ru
page: 65

DISCUSSION

Our results demonstrate an association between genetic polymorphism in exon 5 of the IL-1β gene and MI. Previous studies showed an association of the +3953 (C→T) IL-1b E2 allele with susceptibility to inflammatory bowel disease [11] and primary biliary cirrhosis [16], but no correlation between this genetic polymorphism and susceptibility to alcoholic liver disease [17], hepatitis C virus [18], calcium oxalate stones [19], endometriosis [15] or preeclampsia obstetrics [20].

      Because cytokines and their genes could have a causative or modifying role in atherosclerosis and coronary artery disease (CAD), the+3953 (C→T) polymorphisms of IL-1β was studied in CAD [21]. This polymorphism was not associated with single-vessel or with multi-vessel coronary disease [21]. Our study is the first to report an association between MI in Russians and Tatars of Bashkortostan and the+3953 (C→T) polymorphism of the IL-1β gene in exon 5.

      The genotype frequencies in two Caucasian populations of healthy Russians and of Tatars from Bashkortostan and of other ethnic groups are presented in Table 3. The distribution of genotypes in our control groups was similar to that reported for healthy North American Caucasians (Table 4), but different from that for the Taiwanese and Japanese populations.

      We found no significant differences in the +3953 (C→T) IL-1β polymorphism distribution between Tatar patients with MI and their control group. In Russian patients with MI, the frequency of the E2 allele was higher (OR = 1.45) than in their control group, but the difference was not statistically significant. The E2 allele was present more frequently in Russians with MI in the subgroups with a BMI of >25 but <30 (OR = 1.66), BMI of >30 (OR = 1.89), and LVH (OR = 2.08). Several studies have shown that the E2 allele and E2/E2 genotype of +3953 (C→T) IL-1β polymorphism are associated with increased production of IL-1β [14,15]. However, the association of the E2 allele with increased BMI (>25) and LVH in Russian patients with MI and the association of this allele with higher production of IL-1β is not fully understood, but could be explained by the fact that high level of IL-1β increases production of TNFα, which possibly induces metabolic changes with redistribution of adipose tissue and reduced insulin sensitivity [23].

      In summary, our study shows that the E2/E2 genotype and E2 allele of the +3953 (C→T) IL-1β gene polymorphism may be genetic risk factors for the development of MI in Russian patients with a BMI of >25 and LVH.

 

Table 3. Genotype frequencies (%) of IL-1b gene exon 5 polymorphism in various ethnic populations.

 

 

Genotype

Russian
(n = 116)

Tatar
(n = 129)

Japanese [17]
(n = 218)

Taiwanese [19]
(n = 105)

Taiwanese [22]
(n = 145)

NACa [22]
(n = 200)

E1/E1

61.2

56.6

92.2

97.1

99

57

E1/E2

34.5

35.7

7.8

2.9

1

38

E2/E2

4.3

7.8

0

0

0

6

c2
(p)

0.104
(1.000)

0.324
(0.867)

0.000
(1.000)

0.000
(1.000)

0.000
(1.000)

0.075
(0.974)

 

c2 (p): Correspondence to the expected genotype frequencies.

a NAC: North American Caucasian.

 

 

Table 4. Comparison of ethnic populations with respect to the +3953 (CT) genotype frequencies.

 

Population

c2  (p)

2.Tatar

3.Japanese

4.Taiwanese

5.Taiwanese

 6.NACa

1. Russian

1.427
(0.473)

49.92
(<0.001)

49.49
(<0.001)

61.14
(<0.001)

0.611
(0.733)

2. Tatar

64.57
(<0.001)

50.61
(<0.001)

72.33
(<0.001)

0.698
(0.703)

3. Japanese [17]

2.979
(0.096)

7.233
(0.011)

70.95
(<0.001)

4. Taiwanese [19]

0.679
(0.646)

53.75
(<0.001)

5. Taiwanese [22]

76.66
(<0.001)

6. North American Caucasian [22]

a NAC: North American Caucasian.




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