Association between polymorphism in BMP15 and GDF9 genes and impairing female fecundity in diabetes type 2

Abstract

Background: A shortened reproductive period and earlier menopause have been associated with type 2 diabetes. Growth differentiation factor 9(GDF9) and bone morphogenetic protein 15 (BMP15) gene mutations have been associated with earlier menopause. Therefore, this study aimed to evaluate the association between BMP15 and GDF9 mutations with impairing female fecundity in diabetic patients. The study subjects comprised 90 female diabetic patients and 60 female healthy controls. The physio-biochemical analysis was measured using enzymatic determination. A single-strand conformation polymorphism (SSCP) protocol was utilized to assess the pattern of genetic variations. Results: Genotyping analysis of the BMP15 gene showed a heterogeneous pattern with the presence of two genotypes: AA and AC genotypes. Five novel missense single nucleotide polymorphisms (SNPs) were identified in the BMP15 gene: four SNPs detected in both genotypes, and Met4Leu, a specific SNP, was detected only in the AC genotype. Cumulative in silico tools indicated a highly deleterious effect for the Met4Leu on the mutant protein structure, function, and stability. Diabetes patients showed a significantly higher frequency of genotype AC. The physio-biochemical analysis of fasting plasma glucose (FBG), glycosylated hemoglobin (HbA1c), and luteinizing hormone (LH) were significantly higher (P < 0.05) in AC genotype than AA genotype. Conclusions: The current research provides the first indication regarding the tight association of BMP15 polymorphism with the impairing female fecundity in the diabetic. A pivotal role is played by the novel (Met4Leu) SNP that can be used as a predictor for the impairing female fecundity of diabetes, while no polymorphism was found in exon 4 of the GDF9 gene.

Body mass index and shortened telomere length in middle-aged female and male RUNNING HEAD: Middle-aged and shortened telomere length

“…In higher BMI subjects, this gender difference in TL was revealed among the overweight and obese patients as shown in Table (2). TL was shorter in the overweight and obese patients compared to the control subjects were, the obese male (10.43) of age (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were longer compared to the obese male (9.13) of age (41-50). While obese females (11.13) of age (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were longer compared to the obese female (10.23) of age (41-50).…”

“…TL was shorter in the overweight and obese patients compared to the control subjects were, the obese male (10.43) of age (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were longer compared to the obese male (9.13) of age (41-50). While obese females (11.13) of age (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were longer compared to the obese female (10.23) of age (41-50). Both obese males and females for both age groups were shorter compared to the overweight male and female age groups.…”

“…FSH is also lower in females with obesity and overweight. HPG axis sensitivity may be relatively reduced in obese females that led to a decrease in FSH 38 . This functional impairment happened by increased free fatty acids incorporation into the hypothalamic-pituitary-ovarian axis at the level of the pituitary leading to pausing gonadotropin gene translation affecting LH and FSH synthesis and/or 39 .…”

“…The telomeric probe was revealed by the digoxigenin luminescent procedure after being exposed to X-ray film. As the telomeres shorten with age, all samples were taken at the same age group (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) to determine the telomere length.…”

Sensitivity and applications of the PCR Single-Strand Conformation Polymorphism method

“…Detection of somatic mutations in cancer, genes responsible for hereditary diseases, polymorphisms and other applications are described in detail at Kakavas et al [ 8 – 10 ]. Recent researches in the last 4 years shows dispersion of SSCP method in the above applications: on cancer prognosis [ 11 , 12 ], on asthma disease [ 13 ], on blood groups [ 14 ], on gilbert’s syndrome [ 15 ], on diabetes disease [ 16 ], on respiratory distress syndrome [ 17 ], on infertile men with varicocele [ 18 ], on gastric mucosa [ 19 ], on traditional Chinese medicine [ 20 ], detection of bacterial DNA [ 21 ], identification of trichomonas vaginalis [ 22 ].…”