ADIPOCYTE “FATTY ACID BINDING PROTEIN” GENE POLYMORPHISMS (rs1054135, rs16909196 AND rs16909187) IN JORDANIANS WITH OBESITY AND TYPE 2 DIABETES MELLITUS
El-Ryalat S.W.1, Irshaid Y.M.1*, Abujbara M.2, El-Khateeb M.2, Ajlouni K.M.2
*Corresponding Author: Prof. Yacoub M. Irshaid MD, PhD, Department of Pharmacology, College of Medicine, The University of Jordan, Amman 11942, Jordan. Phone No.: +962 777818284, Fax No.: +962 6 5300820, Email Addresses: y.irshaid@ju.edu.jo
page: 63

DISCUSSION

This study examined the association of (rs1054135, rs16909196 and rs16909187) polymorphisms in the FABP4 gene with the susceptibility to T2DM, obesity, and the relation of these variants with serum concentrations of total cholesterol, LDL, HDL, and triglycerides. The observed minor allele frequency of rs1054135 of 0.09 in the control group is not statistically different from that of the whole studied sample (0.068). The genotypes of the three SNPs are in Hardy-Weinberg equilibrium in our control group and remained so in the whole studied sample. Our findings, showing no association between rs1054135 and both T2DM and obesity, are consistent with what was reported among postmenopausal women, 50-79 years old of multiple ethnicities (Whites, African Americans, Hispanic/Latino Americans, Asian, American- Asian Pacific Islanders) who were enrolled in the “Women’s Health Initiative” study [20]. The study examined 11 SNPs including rs1054135, and the results did not support the association of these SNPs with increased risk of type 2 diabetes mellitus. On the other hand, our results were not in agreement with those of two other studies. A study was performed on 309 children, between 5-7 years of age, in the United States. The children were divided into obese and non-obese groups. Most of the children were white, but the study also included African-Americans. Four SNPs were tested (rs1051231, rs2303519, rs16909233 and rs1054135) and fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA (homeostasis model assessment) was used as a measure of insulin sensitivity. The frequency of rs1054135 allelic variant was increased in obese children (3). A second study, performed among Chinese teenagers in Shanghai, concluded that the rs1054135 minor allele frequency was significantly lower among obese females compared with normal weight females [21]. Concerning rs16909187 and rs16909196, we found that the homozygous wild type genotype (CC) of rs16909187 and the homozygous wild type genotype (AA) of rs16909196 were significantly associated with obesity. However, rs16909187 and rs16909196 minor allele (T) may be protective against obesity. The number of subjects with the homozygous minor allele genotypes is too small to draw conclusions in this regard. The heterozygous minor allele genotypes hint to such protection. The alleles of these two SNPs were not associated with type 2 diabetes mellitus. The haplotypes’ frequencies of rs1054135, rs16909196, and rs16909187 were compared among the various studied groups. Only haplotypes GAC and GTT were related to obesity but not with T2DM. The frequency of the GAC haplotype was higher in the overweight and obese group, while that of GTT haplotype was higher in the control group. The present study showed a significant association between homozygous (GG) and heterozygous (GA) wild type genotypes of rs1054135 and high level of LDL among group 3 (non-diabetic but obese) in comparison with controls (p-value = 0.03). However, there was no significant association between rs1054135 SNP and the serum levels of total cholesterol, HDL and triglycerides among all groups. The rs16909187 and rs16909196 SNPs were not found to be associated with total cholesterol, LDL, HDL, or triglycerides in any of the groups studied. The rs16909187 and rs16909196 SNPs were in linkage disequilibrium among all studied groups. However, none of these two SNPs were in linkage disequilibrium with rs1054135. This agrees with what has been previously reported: rs1054135 has no linkage disequilibrium with other SNPs in FABP4 gene [20]. The limitations of our study are the small sample size studied (397 subjects in the four groups) and the reduced number of females compared to males in all of the groups studied. In conclusion, the 3 SNPs studied followed Hardy- Weinberg equilibrium. There was no association between (rs1054135, rs16909196 and rs16909187) polymorphisms and T2DM. Both rs16909196 and rs16909187 SNPs homozygous wild type genotypes were associated with obesity, while the minor allele genotypes may be protective against obesity. The rs1054135 SNP was not associated with obesity. The rs1054135 SNP was significantly associated with an increase in LDL serum level among obese subjects, but the other two SNPs (rs16909196 and rs16909187) were not associated with any significant changes in lipid profile parameters. There was linkage disequilibrium between the rs16909187 and rs16909196 SNPs in the control and the other studied groups. The rs1054135 SNP was not in linkage disequilibrium with either of the two SNPs. Acknowledgment This research was supported by a grant from the Deanship of Research, The University of Jordan, Amman, Jordan. Endorsement number: 119/2017-2018, Date: 25/04/2018. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.



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