FTO, Abdominal Adiposity, Fasting Hyperglycemia Associated with Elevated HbA1c in Japanese Middle-Aged Women

Abstract

Aim: FTO is the most important polygene for obesity and type 2 diabetes. Our aims were to investigate whether a variant in FTO affects glucose dysregulation through its effect on fat accumulation or distribution, and when and how FTO influences fat accumulation and distribution and glucose dysregulation from birth until midlife. Methods: A total of 454 Japanese female university students (mean age: 20 years) and 132 middleaged women (mean age: 50 years) who were the biological mothers of the students underwent the following: genotyping for rs1558902 in the FTO gene, assessment of fat accumulation and distribution, obesity-related metabolic traits and serum adipokine measurement. A subsample of 364 students reported their weight history since birth. Results: The A allele in rs1558902 was substantially less common in young and middle-aged Japanese women (18 and 17%, respectively) than in the European population (45%). The strong effect of genotype AA on BMI was evident at age 12, 15, 20 and 50 years whereas there was no effect on birth weight. In young and middle-aged women, the variant was strongly associated with higher body weight and fat mass. The effects on abdominal girth, fasting glucose, homeostasis model assessment insulin resistance and HbA1c were evident in mothers but not in students. In addition, genotype AA was associated with increased white blood cell counts and hsCRP in mothers only. Associations with fasting glucose, insulin resistance, and white blood cell counts remained after correction for BMI, abdominal girth and fat mass. In multiple logistic regression analysis, AA homozygote in FTO was associated with higher odds of overweight (BMI ≥ 25 kg/m 2 ) in young (OR 1.73 (95%CI 1.06-30.0)) and middle-aged women (OR 1.73 (95%CI 1.06-30.0)). It was also associated with higher odds of abdominal fat accumulation (abdominal girth ≥ 90 cm, OR 1.73 (95%CI 1.06-30.0)) and fasting hyperglycemia (≥ 100 mg/dL) (OR 1.87 (95%CI 1.05-40.4)) in middle-aged mothers. Conclusion: Despite the small sample size, the low average BMI, and the low risk allele frequency, a genetic variation at the FTO locus was related to greater weight gain before age 12 in Japanese women. At age 20, it was related to general adiposity. In midlife, however, it was related to abdominal adiposity in addition to general adiposity, fasting hyperglycemia, higher HbA1c and subtle systemic inflammation. Fasting hyperglycemia associated with higher HbA1c in midlife was independent of its effects on general and abdominal adiposity.

Association between high sensitivity C-reactive protein and dietary intake in Vietnamese young women

“…The mean hsCRP of the subjects was 1.3 ± 2.9 mg/L, and 9.8% of the subjects were in the high risk hsCRP group, which was similar to the level in young Indian (mean hsCRP levels, 1.3 ± 2.5 mg/L, 12.8% of subjects belonged to the high risk group) [11], but higher than that of other Asian young women [39,40] and Turkish women [41] as well as young women in European countries (mean hsCRP levels, 0.67-0.89 mg/L) [42,43]. In our subjects, hsCRP was highly correlated with many of the metabolic disease parameters such as BMI, WHR, body fat, blood pressure, white blood cell count, triglycerides, and HDL cholesterol, confirming the results of other studies, mostly in middle-aged populations [44,45].…”

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men

“…Genotyping of the SNP was performed using TaqMan SNP Genotyping Assays (Applied Biosystems, Foster City, CA, USA) or a multiplex-polymerase chain reaction (PCR)-invader assay, as described previously [25,29]. In this study, we selected four SNPs (rs8050136, rs9939609, rs1121980, and rs1558902) in the FTO locus; these were the most frequently analyzed SNPs at this locus in the Japanese population [16–20,30–34]. Previous studies have demonstrated that rs8050136, rs9939609, and rs1558902 are in high linkage disequilibrium (LD) with each other and were repeatedly associated with obesity or type 2 diabetes in different ethnicities [31,33,34].…”

“…In this study, we selected four SNPs (rs8050136, rs9939609, rs1121980, and rs1558902) in the FTO locus; these were the most frequently analyzed SNPs at this locus in the Japanese population [16–20,30–34]. Previous studies have demonstrated that rs8050136, rs9939609, and rs1558902 are in high linkage disequilibrium (LD) with each other and were repeatedly associated with obesity or type 2 diabetes in different ethnicities [31,33,34]. First, we examined the LD among these three SNPs in our Japanese population and confirmed that these three SNPs were in absolute LD ( r 2 = 0.99) in our population (S2 Table).…”

Association of Pulse Pressure with Serum TNF-αand Neutrophil Count in the Elderly

“…We evaluated routine chemical parameters, including liver enzymes, glucose, insulin, lipids, and lipoproteins, as previously reported [14, 15] and insulin resistance was evaluated using homeostasis model assessment (HOMA-IR) [16]. …”

“…Adipokines and inflammatory markers were measured as previously reported [14, 15]. They included adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), preheparin lipoprotein lipase (LPL), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-1 (TNF- α ).…”