APOB gene signal peptide deletion polymorphism is not associated with infertility in Indian men

Apolipoprotein B (APOB) plays a key role in lipoprotein metabolism and plasma lipid transport. It has been shown that about two-thirds of male mice heterozygous for ApoB were infertile. Moreover, a 3-codon deletion polymorphism (rs11279109) in the signal peptide region of the APOB gene has been shown to be a risk factor for infertility in Slovenian men, but its association with infertility in Indian men has not been evaluated to date. Hence, in the present study, we have genotyped this polymorphism in 545 Indian men, including 294 infertile and 251 fertile men. Our results show that the distribution of this deletion polymorphism was consistent with the Hardy-Weinberg equilibrium in both infertile and fertile men. No statistically significant difference was observed in the distribution of the APOB signal peptide deletion polymorphism between infertile and fertile men (χ2=0.156, P=.925 for genotypes; χ2=0.015, P=.903 for alleles). Moreover, no significant difference was observed when infertile and fertile men were categorized on the basis of presence (D/D and D/W genotypes) or absence (W/W genotypes) of deletion (odds ratio, 0.955; 95% confidence interval, 0.644-01.418; P=.820). Our study concludes that the APOB gene deletion polymorphism is not a risk factor for the development of infertility in Indian men

Novel variants in UBE2B gene and idiopathic male infertility

The UBE2B gene encodes ubiquitin-conjugating enzyme, which is involved in DNA repair. Ube2b knockout mice were found to be infertile because of structural abnormality of sperm. However, there is no genetic study on the role of the UBE2B gene in human fertility; therefore, the present investigation was designed to study genetic variations in the UBE2B gene and its role in human male infertility. Sequence analyses of the UBE2B gene in 530 infertile (350 azoospermic, 105 oligoasthenoteratozoospermic, and 75 oligoasthenozoospermic) and 300 fertile control men revealed the presence of 5 substitution single-nucleotide polymorphisms (SNPs) in 221 individuals (199 infertile [37.5%] and 22 fertile [7.3%] men). Of these, 2 (g.5197:T>G; g.9157:A>G) of the 5 substitutions were novel and observed only in infertile men. Distribution of haplotypes TA, TG, GA, and GG are not uniform between the patient and the control group of this study. Interestingly, our study suggests that the haplotype TG conferred significantly increased risk for male infertility (odds ratio=5.07, 95% CI=1.29-23.29, p=.007). In silico analysis of SNPs that were specific to infertile men predicted that these SNPs lead to defective splicing by destroying or creating the potential binding site of splicing factors or causing alteration in predicted regulatory sequences. In the light of the above, our study suggests that the UBE2B gene is associated with male infertility in Indian men, hence, providing evidence for additional genetic factors for male infertility

Haplogroup heterogeneity of LHON patients carrying the m.14484T>C mutation in India

Purpose: To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber Hereditary Optic Neuropathy (LHON) patients carrying the m.14484T>C mutation. Methods: Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. Results: In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e. F1c1, M31a, U2a, M*, I1, M6, M3a1 and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. Conclusions: Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease

LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations

In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae

Assessment of Feasibility and Patency of below the Knee Atherectomy Using the 1.5 mm Phoenix Catheter—A Retrospective Study

Background and Objectives: Peripheral arterial disease (PAD) contains a significant proportion of patients whose main pathology is located in the infragenicular arteries. The treatment of these patients requires a deliberate consideration due to the threat of possible complications of an intervention. In this retrospective study, the feasibility of a below-the-knee atherectomy (BTKA) via a 1.5 mm Phoenix atherectomy catheter and the patient outcome over the course of 6 months are investigated. Materials and Methods: The data of patients suffering from PAD with an infragenicular pathology treated via 1.5 mm Phoenix™ atherectomy catheter between March 2021 and February 2022 were retrospectively analyzed. Prior to the intervention, after 2 weeks and 6 months, the PAD stages were graded and ankle-brachial-indeces (ABI) were measured. Results: The study shows a significant improvement of ABI, both after 2 weeks and 6 months. Additionally, the number of PAD stage IV patients decreased by 15.2% over the course of 6 months, and 18.2% of the patients improved to PAD stage IIa. Only one bleeding complication on the puncture side occurred over the whole study, and no other complications were observed. Conclusions: Phoenix™ atherectomy usage in the BTKA area seems to be feasible and related to a favorable outcome in this retrospective study

Genetic evidence of TAP1 gene variant as a susceptibility factor in Indian leprosy patients

The heterodimeric transporter associated with antigen processing (TAP) gene loci is known to play a vital role in immune surveillance. We investigated a possible association of gene polymorphisms both in TAP1 and TAP2 in a cohort of clinically classified leprosy patients (n = 222) and in ethnically matched controls (n = 223). The TAP1 and TAP2 genes were genotyped for four single nucleotide polymorphisms TAP1 (rs1057141 Iso333Val and rs1135216 Asp637Gly) and TAP2 (rs2228396 Ala565Thr and rs241447 Ala665Thr) by direct sequencing and ARMS-PCR. The minor allele of TAP1 637G contributes to an increased risk to leprosy compared to controls (OR: 1.68, 95% CI 1.2–2.36, P = 0.0057). An increased risk for the variant minor allele of the TAP1 637G to multibacillary (BL + LL) or paucibacillary (BT + TT) infections was also observed [multibacillary vs. controls (OR: 1.56, 95% CI 1.07–2.28, P = 0.054); paucibacillary vs. controls (OR: 1.92, 95% CI 1.21–3.01, P = 0.013)]. In the dominant model, the genotypes of the TAP1 rs1135216AG + GG additionally contributed to an increased risk. Overall our findings demonstrate that the TAP1 gene variant (rs1135216 Asp637Gly) influences the susceptibility to clinically classified leprosy patients in Indian population

Clinical and neuroimaging features in two children with mutations in the mitochondrial ND5 gene

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT-ND5) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic–genetic testing and prognostication

Audiological manifestations in mitochondrial encephalomyopathy lactic acidosis and stroke like episodes (MELAS) syndrome

Objectives: Reports of audiological manifestations in specific subgroups of mitochondrial disorders are limited. This study aims to describe the audiological findings in patients with MELAS syndrome and m.3243A>G mutation. Patients & Methods: Audiological evaluation was carried out in eight patients with confirmed MELAS syndrome and m.3243A>G mutation. The evaluation included a complete neurological evaluation, pure tone audiometry (n = 8), otoacoustic emissions (n = 8) and brainstem evoked response audiometry (n = 6), magnetic resonance imaging (n = 8) and muscle biospy (n = 6). Results: Eight patients (Age range: 5–45 years; M:F-1:3) including six children and two adults underwent formal audiological evaluation. Five patients had hearing loss; of these two had “subclinical hearing loss”, one had moderate and two had severe hearing loss. The abnormalities included abnormal audiometry (n = 5), otoacoustic emission testing (n = 7) and absent brainstem auditory evoked responses (n = 1). The findings were suggestive of cochlear involvement in four and retrocochlear in one. Conclusions: This study shows that hearing loss of both cochlear and retrocochlear origin occurs in patients with MELAS and may be subclinical. Early referrals for audiological evaluation is warranted to recognize the subclinical hearing loss in these patients. The therapeutic implications include early interventions in the form of hearing aids, cochlear implants and cautioning the physicians for avoidance of aminoglycosides