Adiponectin gene variant RS rs266729: Relation to lipid profile changes and circulating adiponectin after bariatric surgery

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

“…De Luis et al (2018) also reported that rs266729 CC homozygotes had significantly greater adiponectin increases than G-carriers when 149 morbidly obese patients lost an average of 41.9 kg during the three years following biliopancreatic diversion surgery ( Fig. 5D histogram, 33.2 ± 0.4 vs. 4.7 ± 0.2 ng/ml; P = 0.01).…”

“… Precision medicine perspective of ADIPOQ genotype-specific adiponectin differences (histogram inserts) vs. quantile-dependent expressivity perspective (line graphs showing larger genetic effect size when average adiponectin concentrations were high) for: (A) Kang et al’s 2005 report ( Kang et al, 2005 ) on the effect of 12-weeks 4 mg/day of rosiglitazone treatment in 25 GG rs2241766 homozygotes and 86 T-allele carriers with T2DM; (B) de Luis et al’s 2020 report ( De Luis et al, 2020 ) on the pooled effect of switching from a basal to a 27%- or 38%-fat hypocaloric diet in 169 rs266729 CC homozygotes and 114 G-allele carriers; (C) Aller et al’s 2019 report ( Aller et al, 2019 ) on the pooled effect of switching from a basal to a standard or high-protein extreme hypocaloric diet in 122 rs1501299 GG homozygotes than 147 T-allele carriers; (D) De Luis et al’s 2018 report ( De Luis et al, 2018 ) on the effect of 41.9 kg weight loss from biliopancreatic diversion surgery in 84 rs266729 CC homozygote and 65 G-allele carriers who were morbidly obesity. The histograms and line graphs were derived from the mean concentrations presented in the original manuscripts.…”

“…We analyzed untransformed adiponectin concentrations because quantile-regression does not require normality, and no biological rationale has been proposed for their logarithmic transformation. Parenthetically, the significant interactions reported by Kang et al (2005), De Luis et al (2020), De Luis et al (2018), De Luis et al (2019), Divella et al (2017), Aller et al (2019) and Garcia-Garcia et al (2014) were all based on untransformed adiponectin concentrations.…”

“…, increase with rosiglitazone treatment (Kang et al, 2005), increase during postprandial lipemia (Musso et al, 2008), and decrease with adiposity (De Luis et al, 2020;De Luis et al, 2018;De Luis et al, 2019;Corbi et al, 2019;Divella et al, 2017;Garcia-Garcia et al, 2014;Berthier et al, 2005;Aller et al, 2019). It remains to be determined whether the heritability of adiponectin concentrations is quantile-dependent, and whether this produces significant heritability differences by sex, genotype-specific increases during rosiglitazone treatment or postprandial lipemia, and gene-environment interactions by adiposity level.…”

“…An important consequence of quantile-dependent expressivity is that the selection of subjects for characteristics that distinguish high vs. low phenotypes can yield different genetic effects ( Williams, 2012 ; Williams, 2020e ). Adiponectin concentrations are greater in women than men ( Liu et al, 2008 ; Hicks et al, 2007 ; Comuzzie et al, 2001 ; Vaughan et al, 2015 ; Chuang et al, 2004 ; Dosaev, Prakash & Livshits, 2014 ; Henneman et al, 2010 ; Guo et al, 2006 ; Ling, Waterworth et al, 2009 ; Vasseur et al, 2002 ; Cesari et al, 2007 ; Berra et al, 2006 ), increase with rosiglitazone treatment ( Kang et al, 2005 ), increase during postprandial lipemia ( Musso et al, 2008 ), and decrease with adiposity ( De Luis et al, 2020 ; De Luis et al, 2018 ; De Luis et al, 2019 ; Corbi et al, 2019 ; Divella et al, 2017 ; Garcia-Garcia et al, 2014 ; Berthier et al, 2005 ; Aller et al, 2019 ). It remains to be determined whether the heritability of adiponectin concentrations is quantile-dependent, and whether this produces significant heritability differences by sex, genotype-specific increases during rosiglitazone treatment or postprandial lipemia, and gene-environment interactions by adiposity level.…”