Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S.Hispanics/Latinos

Abstract

Objective We examined associations of IRS1 genetic variation with adiposity and metabolic profile in US Hispanic/Latino individuals of diverse backgrounds. Methods Previously genome-wide association study identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5232 men; 7515 women) from the Hispanic Community Health Study/Study of Latinos. Results The C-allele (frequency=26%) of rs2943650 was significantly associated with higher BF% in overall (β=0.34±0.11% per allele; P=0.002) and in women (β=0.41±0.14% per C-allele; P=0.003), but not in men (β=0.28±0.18% per C-allele; P=0.11), though there was no significant sex-difference. Using the inverse-normal-transformed data to compare effect sizes, we found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β=0.054±0.018SD vs β=0.008±0.011SD per C-allele; P=0.03). We also observed that the BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, HOMA-IR, Hemoglobin A1c and triglycerides, and higher HDL-cholesterol (P<0.05). Conclusions Our study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in US Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared to European women.

IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits

“…Additionally, IRS1 mRNA expression data were extracted from a previous data set 14 . Although non-significant, which is most likely due to the small sample size for genetic association studies, our data are in line with others 1 , 25 . We found among T allele carriers (major allele) a favourable anthropometric pattern, which is however combined with more unhealthy metabolic variables compared to C allele carriers.…”

Prevalence of self‐reported obesity among diverse Latino adult populations in New York City, 2013–2017

“…The prevalence of obesity by specific Latino group is unclear as the majority of obesity research ignores the country of origin or has primarily involved Mexican Americans 2,6‐8 . A limited number of obesity studies have started to report on country‐of‐origin differences for some Latino groups (e.g., Mexicans, Puerto Ricans, Cubans, and Dominicans) and combined regional groups (i.e., Central American and South American) 3,6,8‐22 . According to these studies, Latinos of all backgrounds experience high rates of obesity 3,6,8‐11,13‐18 .…”

“…Indeed, emerging evidence suggests that country of origin is an important factor to understand obesity 3,6,8‐22 . Recent studies suggest that some Latino immigrants may no longer be arriving with healthy weight status to the U.S. because Latin American countries are undergoing epidemiologic 23,24 and nutrition transitions 25,26 .…”

“…For example, Mexico has some of the highest obesity and overweight prevalence in the world currently 27‐29 . These studies are encouraging more research to limit overgeneralization of Latinos in the U.S. and further explore the heterogeneity of Latinos in terms of socio‐demographic characteristics, diet, physical activity (PA), obesity and comorbid conditions 3,6,8‐22 . The present study responded to this call by examining and comparing the prevalence of obesity in a large and diverse sample of Latino immigrants born in Latin America but residing in NYC.…”

Associação de variantes em >i<MC3R, MC4R, IRS1>/i< e >i<IRS2>/i< com obesidade e marcadores metabólicos, inflamatórios e adipocinas

“…Variantes intergênicas rs2943650, rs2943634 e rs2943641 foram associadas com percentagem de gordura corporal, em mulheres hispânicas e latinas dos Estados Unidos (QI et al, 2016). Nesse estudo, a variante rs2943650 foi associada com adiposidade e perfil metabólico favorável.…”