Interleukin-1 Receptor Antagonist and Interleukin-4 Genes Variable Number Tandem Repeats Are Associated with Adiposity in Malaysian Subjects

Abstract

Interleukin-1 receptor antagonist ( IL1RA ) intron 2 86 bp repeat and interleukin-4 ( IL4 ) intron 3 70 bp repeat are variable number tandem repeats (VNTRs) that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher overall adiposity, relative to those having the I/I genotype or I allele, respectively, even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.002</mml:mn></mml:math>); II allele = 5.78 (CI = 1.73, 19.29;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.004</mml:mn></mml:math>)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.03</mml:mn></mml:math>)]. Individuals with IL1RA II allele had significantly higher TBF than those with I allele (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn fontstyle="italic">31.79</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">2.52</mml:mn></mml:math> versus <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mn fontstyle="italic">23.51</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">0.40</mml:mn></mml:math>;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.005</mml:mn></mml:math>). Taken together, IL1RA intron 2 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.