Adiponectin Receptor gene Polymorphisms are Associated with Kidney Function in Elderly Japanese Populations.

AIM: Adiponectin exhibits its biological effects through adiponectin receptors (AdipoR1 and AdipoR2), which are distributed in the kidneys, and activation of those receptors could prevent or ameliorate diabetic nephropathy. This study aimed to evaluate the associations between AdipoR single nucleotide polymorphisms (SNPs) and kidney function in an elderly Japanese population. METHODS: A total of 271 elderly Japanese volunteers underwent anthropometric and laboratory tests (cystatin C-based eGFR and total and high molecular weight adiponectin levels at baseline and a follow-up visit). Genotype data were obtained for the selected 7 and 5 AdipoR1 and AdipoR2 SNPs, respectively. RESULTS: In a cross-sectional analysis at baseline, we found a significant association between the AdipoR2 SNP rs12230440 and kidney function; eGFRcys tended to increase as the number of carriers of T alleles increased after adjustment for covariates and Bonferroni correction, although the association of the SNP and annual eGFR decline could not be identified in the longitudinal data. Regarding the variants rs16850797, rs11061925, and rs10773983, each of the allele G, allele C, and allele G showed nominally significant associations with higher eGFRcys. However, this failed to reach significance after Bonferroni correction. CONCLUSION: Here, an AdipoR2 SNP was associated with kidney function, suggesting that the effects of this polymorphism on adiponectin receptor may affect kidney function in the elderly Japanese population.

Haplotype-based case-control study of estrogen receptor alpha (ESR1) gene and pregnancy-induced hypertension.

Hypotheses about pregnancy-induced hypertension (PIH) have been proposed to explain the vascular damage that characterizes this disease. Reports indicate that estrogens and estrogen receptors play important physiological roles in cardiovascular diseases. There have been studies examining the association between coronary artery disease and the estrogen receptor alpha (ESR1) gene. The aim of the present work was to assess the association between PIH and single-nucleotide polymorphisms (SNPs) in the human ESR1 gene, by conducting a haplotype-based case-control study. Based on a database search at the web site of the National Center of Biotechnology Information, we chose five SNPs in the human ESR1 gene, and performed an association study using 95 PIH patients and 200 age-matched non-PIH subjects. The frequency of rs2881766 genotypes and alleles differed significantly between the two groups. There was no significant difference in overall distribution of genotypes or alleles of the other four SNPs. The T allele of rs2881766 was significantly more prevalent in the PIH group than in the non-PIH group. Haplotype-based case-control analysis revealed that there was a significant difference in overall distribution of the combinations rs2881766-rs1643821-rs988328 and rs2881766-rs1643821 between the PIH group and the non-PIH group (all or body mass index [BMI]-matched). One susceptibility haplotype for PIH and two resistance haplotypes for PIH were revealed by comparison between the PIH group and the non-PIH (BMI-matched) control group. In conclusion, the T allele of rs2881766 could be a useful genetic marker of PIH. The G-A-T haplotype of rs2881766-rs1643821-rs988328 and the G-A haplotype of rs2881766-rs1643821 appear to be resistance markers of PIH.

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (ß = -0.23; P = .71, ß = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (ß = -0.50; P = .46, ß = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption.

Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.

The Deterioration of the Glycemic Profile during Hormone Replacement Therapy in a Patient with Fulminant Type 1 Diabetes.

Although most women with type 1 diabetes experience the normal transition to menopause, there is little information about the impact of hormone replacement therapy on their glycemic profiles. A 54-year-old postmenopausal woman with fulminant type 1 diabetes was admitted to our hospital due to diabetic ketoacidosis. She was treated with fluid replacement and a continuous insulin infusion. Thereafter, her glycemic profile was well maintained by daily multiple insulin injections. However, her glycemic profiles immediately deteriorated following the administration of progesterone in hormone replacement therapy. This transient deterioration implies that external progesterone can lead to the deterioration of glycemic profiles in postmenopausal women with type 1 diabetes.